We present the case of 72–year-old male with metastatic de-differentiated chondrosarcoma (“DDCS”). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies.
Case
This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi-targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET-CT scan revealed a 10cmx5cm destructive intra-osseous lesion of the proximal humerus, markedly FDG-avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high-grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET-CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis.
Conclusion
This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.
{"title":"A Case Report of Promising Response to Combination Therapy With an Immune Checkpoint Inhibitor (Pembrolizumab) and Multi-Targeted Tyrosine Kinase Inhibitor (Pazopanib) in Metastatic De-Differentiated Chondrosarcoma","authors":"Matthew Youssef, Peter Grimison","doi":"10.1002/cnr2.70426","DOIUrl":"10.1002/cnr2.70426","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We present the case of 72–year-old male with metastatic de-differentiated chondrosarcoma (“DDCS”). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi-targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET-CT scan revealed a 10cmx5cm destructive intra-osseous lesion of the proximal humerus, markedly FDG-avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high-grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET-CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enfortumab vedotin (EV) has demonstrated clinical benefits as a third-line monotherapy after chemotherapy and immune checkpoint inhibitors and is currently established, in combination with pembrolizumab, as a first-line standard therapy for metastatic urothelial carcinoma (mUC). However, dermatologic adverse events (DAEs) are common and may necessitate treatment interruption. While EV rechallenge is often considered, evidence regarding the recurrence and management of DAEs after rechallenge is limited.
Aims
To analyze the incidence, timing, and severity of DAEs following EV rechallenge and assess the impact of dose modifications and initial inpatient versus outpatient management on clinical outcomes.
Methods and Results
This retrospective observational study included patients with mUC who received EV at a single institution between January 2022 and December 2024. Of the 48 patients treated with EV, 36 (75.0%) developed DAEs, with a median onset of 11 days. Twenty patients resumed EV after interruption due to DAEs; 13 (65%) experienced recurrence. Recurrent DAEs tended to be of lower grade than the initial events and to be similar to the initial episode in terms of the type of DAEs. Early-onset (≤ 7 days) DAEs were more likely to progress to grade ≥ 3. Although inpatient management enabled earlier detection and intervention, it did not reduce the incidence of severe toxicity compared to outpatient care.
Conclusion
DAEs frequently recur after EV rechallenge but are typically less severe than the initial episode. Early-onset DAEs may predict severe toxicity, underscoring the need for close monitoring and proactive management. Prospective studies are warranted to optimize rechallenge strategies and improve the safety of EV therapy.
{"title":"Outcomes and Management of Dermatologic Toxicity Following Enfortumab Vedotin Rechallenge in Patients With Metastatic Urothelial Carcinoma: A Retrospective Single-Center Study","authors":"Takashi Kawahara, Yoshiyuki Nagumo, Akane Yamaguchi, Kazuki Hamada, Kozaburo Tanuma, Satoshi Nitta, Masanobu Shiga, Atsushi Ikeda, Shuya Kandori, Akio Hoshi, Hiroyuki Nishiyama","doi":"10.1002/cnr2.70466","DOIUrl":"10.1002/cnr2.70466","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Enfortumab vedotin (EV) has demonstrated clinical benefits as a third-line monotherapy after chemotherapy and immune checkpoint inhibitors and is currently established, in combination with pembrolizumab, as a first-line standard therapy for metastatic urothelial carcinoma (mUC). However, dermatologic adverse events (DAEs) are common and may necessitate treatment interruption. While EV rechallenge is often considered, evidence regarding the recurrence and management of DAEs after rechallenge is limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To analyze the incidence, timing, and severity of DAEs following EV rechallenge and assess the impact of dose modifications and initial inpatient versus outpatient management on clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This retrospective observational study included patients with mUC who received EV at a single institution between January 2022 and December 2024. Of the 48 patients treated with EV, 36 (75.0%) developed DAEs, with a median onset of 11 days. Twenty patients resumed EV after interruption due to DAEs; 13 (65%) experienced recurrence. Recurrent DAEs tended to be of lower grade than the initial events and to be similar to the initial episode in terms of the type of DAEs. Early-onset (≤ 7 days) DAEs were more likely to progress to grade ≥ 3. Although inpatient management enabled earlier detection and intervention, it did not reduce the incidence of severe toxicity compared to outpatient care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DAEs frequently recur after EV rechallenge but are typically less severe than the initial episode. Early-onset DAEs may predict severe toxicity, underscoring the need for close monitoring and proactive management. Prospective studies are warranted to optimize rechallenge strategies and improve the safety of EV therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>To investigate the significance of detecting folate receptor-positive circulating tumor cells (FR + CTC) in colorectal cancer patients and to analyze their correlation with the expression of conventional tumor markers (CEA, CA199, CA125).</p> </section> <section> <h3> Methods and Results</h3> <p>A retrospective collection of preoperative FR + CTC values from patients in the Gastrointestinal Surgery Department of Henan Provincial People's Hospital between July 2021 and May 2023 was conducted. The area under the ROC curve was used to assess the accuracy of FR + CTC values and the expression levels of conventional tumor markers (CEA, CA199, CA125) in diagnosing colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4). Spearman correlation analysis was used to study the correlation between FR + CTC values and the expression levels of CEA, CA199, and CA125. Non-parametric tests were used to study the differences in CTC values, CEA, CA199, and CA125 among different types of colorectal cancer patients. A total of 273 colorectal cancer patients with preoperative FR + CTC detection were included in the study. Among these, 19 patients (7.0%) had peritoneal metastasis. The areas under the ROC curve for diagnosing colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4) using FR + CTC were 0.828, 0.617, 0.651, 0.642, and 0.622, respectively, all of which were higher than those of conventional tumor markers (CEA, CA199, CA125). The optimal FR + CTC cut-off value for diagnosing peritoneal metastasis was 14.0 FU/3 mL, with a sensitivity of 80.5% and a specificity of 85.2%. There was a statistically significant correlation between FR + CTC values and CA125 expression levels (correlation coefficient <i>R</i> = 0.15, <i>p</i> = 0.015), while no significant correlation was found between FR + CTC values and the expression levels of CEA and CA199. The detection values of FR + CTC were higher in colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4), with statistically significant differences (<i>p</i> < 0.05).</p> </section> <section> <h3> Conclusion</h3> <p>FR + CTC values can serve as a new tumor marker for colorectal cancer patients, offering stronger clinical guidance than traditional gastrointestinal tumor markers (CEA, CA199, CA125). Future research should focus on validating these results in multicenter pr
{"title":"Significance and Correlation Analysis of Folate Receptor-Positive Circulating Tumor Cells (FR + CTC) in Colorectal Cancer Patients","authors":"Renwang Hu, Aofeng Lan, Dan Li, Can Liu","doi":"10.1002/cnr2.70453","DOIUrl":"10.1002/cnr2.70453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To investigate the significance of detecting folate receptor-positive circulating tumor cells (FR + CTC) in colorectal cancer patients and to analyze their correlation with the expression of conventional tumor markers (CEA, CA199, CA125).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A retrospective collection of preoperative FR + CTC values from patients in the Gastrointestinal Surgery Department of Henan Provincial People's Hospital between July 2021 and May 2023 was conducted. The area under the ROC curve was used to assess the accuracy of FR + CTC values and the expression levels of conventional tumor markers (CEA, CA199, CA125) in diagnosing colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4). Spearman correlation analysis was used to study the correlation between FR + CTC values and the expression levels of CEA, CA199, and CA125. Non-parametric tests were used to study the differences in CTC values, CEA, CA199, and CA125 among different types of colorectal cancer patients. A total of 273 colorectal cancer patients with preoperative FR + CTC detection were included in the study. Among these, 19 patients (7.0%) had peritoneal metastasis. The areas under the ROC curve for diagnosing colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4) using FR + CTC were 0.828, 0.617, 0.651, 0.642, and 0.622, respectively, all of which were higher than those of conventional tumor markers (CEA, CA199, CA125). The optimal FR + CTC cut-off value for diagnosing peritoneal metastasis was 14.0 FU/3 mL, with a sensitivity of 80.5% and a specificity of 85.2%. There was a statistically significant correlation between FR + CTC values and CA125 expression levels (correlation coefficient <i>R</i> = 0.15, <i>p</i> = 0.015), while no significant correlation was found between FR + CTC values and the expression levels of CEA and CA199. The detection values of FR + CTC were higher in colorectal cancer patients with peritoneal metastasis, lymph node metastasis, vascular invasion, nerve invasion, and tumor penetration of the serosal layer (T3-4), with statistically significant differences (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FR + CTC values can serve as a new tumor marker for colorectal cancer patients, offering stronger clinical guidance than traditional gastrointestinal tumor markers (CEA, CA199, CA125). Future research should focus on validating these results in multicenter pr","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12817193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lenvatinib-related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.
Aims
We aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.
Methods and Results
A retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib-related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).
Conclusion
Initiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib-related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib-related hypothyroidism.
{"title":"Clinical Course and Risk Factors of Lenvatinib-Related Hypothyroidism in Hepatocellular Carcinoma: A Retrospective Cohort Study","authors":"Chihiro Shiraishi, Hideo Kato, Yuki Asai, Takuya Iwamoto","doi":"10.1002/cnr2.70461","DOIUrl":"10.1002/cnr2.70461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lenvatinib-related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib-related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Initiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib-related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib-related hypothyroidism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12819047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nonsmall cell lung cancer (NSCLC) with mesenchymal-epithelial transition exon 14 skipping mutation (METex14) represents a distinct molecular subtype with limited therapeutic options. Selective MET tyrosine kinase inhibitors (MET-TKIs) such as tepotinib, capmatinib, and gumarontinib have improved outcomes, but toxicities frequently limit their use. Previous case reports have described sequential rechallenge with two MET-TKIs and, in rare cases, with three agents including an investigational drug. To our knowledge, this is the first reported case worldwide of sequential treatment with all three MET-TKIs currently approved in Japan—tepotinib, capmatinib, and gumarontinib.
Case
We report a 72-year-old man with METex14-positive NSCLC who underwent surgery and adjuvant chemotherapy, later developing pleural dissemination. Tepotinib was discontinued after 2 months due to Grade 3 interstitial lung disease (ILD). Following chemotherapy and immune checkpoint inhibitors, capmatinib was introduced but stopped within 10 days for fever, mucositis, and possible ILD. Gumarontinib was subsequently initiated, but treatment was interrupted on Day 36 due to Grade 2 hepatotoxicity before resumption at a reduced dose.
Conclusions
Although all three MET-TKIs share similar mechanisms of action, they exhibit differing toxicity profiles. In this case, treatment discontinuation was not due to ILD recurrence but rather to distinct non-ILD adverse events. Furthermore, the toxicities experienced by the patient varied between agents, suggesting that rechallenge may remain a viable strategy depending on individual tolerance. Careful toxicity monitoring and personalized risk assessment are essential when considering sequential MET-TKI therapy.
{"title":"Challenges and Limitations of Sequential MET-TKI Therapy in METex14- Positive NSCLC With a Focus on Non-ILD Toxicities: A Case Report","authors":"Akina Nigi, Toshikazu Kumasa, Keisuke Iwamoto, Hidetoshi Itani, Shigeto Kondou, Junji Uraki","doi":"10.1002/cnr2.70458","DOIUrl":"10.1002/cnr2.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nonsmall cell lung cancer (NSCLC) with mesenchymal-epithelial transition exon 14 skipping mutation (METex14) represents a distinct molecular subtype with limited therapeutic options. Selective MET tyrosine kinase inhibitors (MET-TKIs) such as tepotinib, capmatinib, and gumarontinib have improved outcomes, but toxicities frequently limit their use. Previous case reports have described sequential rechallenge with two MET-TKIs and, in rare cases, with three agents including an investigational drug. To our knowledge, this is the first reported case worldwide of sequential treatment with all three MET-TKIs currently approved in Japan—tepotinib, capmatinib, and gumarontinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We report a 72-year-old man with METex14-positive NSCLC who underwent surgery and adjuvant chemotherapy, later developing pleural dissemination. Tepotinib was discontinued after 2 months due to Grade 3 interstitial lung disease (ILD). Following chemotherapy and immune checkpoint inhibitors, capmatinib was introduced but stopped within 10 days for fever, mucositis, and possible ILD. Gumarontinib was subsequently initiated, but treatment was interrupted on Day 36 due to Grade 2 hepatotoxicity before resumption at a reduced dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although all three MET-TKIs share similar mechanisms of action, they exhibit differing toxicity profiles. In this case, treatment discontinuation was not due to ILD recurrence but rather to distinct non-ILD adverse events. Furthermore, the toxicities experienced by the patient varied between agents, suggesting that rechallenge may remain a viable strategy depending on individual tolerance. Careful toxicity monitoring and personalized risk assessment are essential when considering sequential MET-TKI therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemotherapy resistance in colorectal cancer (CRC) is often mediated by enhanced DNA damage repair (DDR). Transmembrane protein TMEM59L is implicated in cancer progression, but its role in CRC chemoresistance is unclear. We investigated whether TMEM59L regulates 5-fluorouracil (5-FU) sensitivity through PTPRN-mediated DDR.
Aims
This study aimed to investigate the role of TMEM59L in regulating PTPRN-mediated DNA damage repair and its impact on 5-FU sensitivity in colorectal cancer, with the goal of identifying potential therapeutic targets to overcome chemoresistance.
Methods and Results
Bioinformatics analyses assessed TMEM59L/PTPRN expression and prognosis in CRC cohorts. Gain- and loss-of-function experiments were conducted in CRC cell lines (HCT116, SW480) and their 5-FU-resistant derivatives. Cell proliferation, migration, invasion, apoptosis, DNA damage, and reactive oxygen species (ROS) were measured. Protein interactions were examined by Western blot and immunofluorescence. A xenograft model in nude mice validated the TMEM59L/PTPRN axis on tumor growth, stemness, and EMT markers. TMEM59L expression was elevated in metastatic lesions and associated with poor CRC patient survival. Functionally, TMEM59L promoted malignant behaviors and epithelial–mesenchymal transition. It was upregulated in 5-FU-resistant cells and non-responsive patients. TMEM59L knockdown sensitized cells to 5-FU, increasing ROS, DNA damage, and apoptosis, while its overexpression induced resistance. Mechanistically, TMEM59L regulated 5-FU-induced DNA damage and ROS through PTPRN. PTPRN overexpression reversed the sensitization caused by TMEM59L silencing. In vivo, TMEM59L knockdown enhanced 5-FU's antitumor effect, which was counteracted by PTPRN overexpression.
Conclusion
The TMEM59L/PTPRN axis is a key regulator of DDR and 5-FU resistance in CRC. TMEM59L promotes chemoresistance via PTPRN by enhancing DNA repair and reducing ROS-mediated apoptosis. Targeting this pathway may offer a novel strategy to overcome 5-FU resistance.
{"title":"Transmembrane Protein TMEM59L Modulates 5-FU Resistance via PTPRN-Mediated DNA Damage Repair in Colorectal Cancer","authors":"Wenzhi Jin, Qiang Ma, Zenghui Ma, Jianhua Hou, Fenming Wang, Huiqing Kang, Chen Wang, Xiaoliang Wang, Feng Liu","doi":"10.1002/cnr2.70448","DOIUrl":"10.1002/cnr2.70448","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chemotherapy resistance in colorectal cancer (CRC) is often mediated by enhanced DNA damage repair (DDR). Transmembrane protein TMEM59L is implicated in cancer progression, but its role in CRC chemoresistance is unclear. We investigated whether TMEM59L regulates 5-fluorouracil (5-FU) sensitivity through PTPRN-mediated DDR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to investigate the role of TMEM59L in regulating PTPRN-mediated DNA damage repair and its impact on 5-FU sensitivity in colorectal cancer, with the goal of identifying potential therapeutic targets to overcome chemoresistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Bioinformatics analyses assessed TMEM59L/PTPRN expression and prognosis in CRC cohorts. Gain- and loss-of-function experiments were conducted in CRC cell lines (HCT116, SW480) and their 5-FU-resistant derivatives. Cell proliferation, migration, invasion, apoptosis, DNA damage, and reactive oxygen species (ROS) were measured. Protein interactions were examined by Western blot and immunofluorescence. A xenograft model in nude mice validated the TMEM59L/PTPRN axis on tumor growth, stemness, and EMT markers. TMEM59L expression was elevated in metastatic lesions and associated with poor CRC patient survival. Functionally, TMEM59L promoted malignant behaviors and epithelial–mesenchymal transition. It was upregulated in 5-FU-resistant cells and non-responsive patients. TMEM59L knockdown sensitized cells to 5-FU, increasing ROS, DNA damage, and apoptosis, while its overexpression induced resistance. Mechanistically, TMEM59L regulated 5-FU-induced DNA damage and ROS through PTPRN. PTPRN overexpression reversed the sensitization caused by TMEM59L silencing. In vivo, TMEM59L knockdown enhanced 5-FU's antitumor effect, which was counteracted by PTPRN overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The TMEM59L/PTPRN axis is a key regulator of DDR and 5-FU resistance in CRC. TMEM59L promotes chemoresistance via PTPRN by enhancing DNA repair and reducing ROS-mediated apoptosis. Targeting this pathway may offer a novel strategy to overcome 5-FU resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autumn Beavers, Elizabeth F. Msoka, Irene Masue, Theresia Mwakyembe Mwansasu, Ayesiga Herman, Blandina T. Mmbaga, Lily Gutnik
Background
In sub-Saharan Africa, traditional healers often serve as primary healthcare providers and are the first point of contact for patients. Given this, they are uniquely positioned to aid in early breast cancer detection. To evaluate this, we implemented a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.
Aims
To implement a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.
Methods
We conducted a breast cancer training program in Tanzania among rural registered traditional healers. Knowledge acquisition was assessed through pretest and posttest surveys.
Results
Three male and three female rural traditional healers (average age: 53) participated in the training, with 67% having no prior formal breast cancer training, though 83% reported some breast cancer awareness. Pre- and post-training assessments showed an increase in breast cancer knowledge, with median scores rising from 41% to 74% (p = 0.01). All participants found the training valuable and felt empowered to serve as community health advocates, with widespread consensus that they would prioritize referring patients with suspicious breast findings to the hospital rather than attempting to treat.
Conclusion
Traditional healers, as trusted community figures and primary healthcare providers, offer a promising solution to bridging gaps in early breast cancer detection in Tanzania. Enhancing their breast cancer knowledge and equipping them with the skills to identify suspicious breast findings provides a scalable strategy for improving early detection in resource-limited settings.
{"title":"Breast Health Training Program for Traditional Healers: A Pathway to Early Breast Cancer Detection in Tanzania","authors":"Autumn Beavers, Elizabeth F. Msoka, Irene Masue, Theresia Mwakyembe Mwansasu, Ayesiga Herman, Blandina T. Mmbaga, Lily Gutnik","doi":"10.1002/cnr2.70377","DOIUrl":"10.1002/cnr2.70377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In sub-Saharan Africa, traditional healers often serve as primary healthcare providers and are the first point of contact for patients. Given this, they are uniquely positioned to aid in early breast cancer detection. To evaluate this, we implemented a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To implement a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a breast cancer training program in Tanzania among rural registered traditional healers. Knowledge acquisition was assessed through pretest and posttest surveys.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three male and three female rural traditional healers (average age: 53) participated in the training, with 67% having no prior formal breast cancer training, though 83% reported some breast cancer awareness. Pre- and post-training assessments showed an increase in breast cancer knowledge, with median scores rising from 41% to 74% (<i>p</i> = 0.01). All participants found the training valuable and felt empowered to serve as community health advocates, with widespread consensus that they would prioritize referring patients with suspicious breast findings to the hospital rather than attempting to treat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Traditional healers, as trusted community figures and primary healthcare providers, offer a promising solution to bridging gaps in early breast cancer detection in Tanzania. Enhancing their breast cancer knowledge and equipping them with the skills to identify suspicious breast findings provides a scalable strategy for improving early detection in resource-limited settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole J. Newman-Hung, Kameel Khabaz, Michaela Juels, Giovanni Gamalong, Daniel Chiou, Bailey Mooney, Nicholas M. Bernthal, Lauren E. Wessel
Background
Soft tissue sarcomas (STS) of the upper extremity (UE) are uncommon and may require complex surgical management. Socioeconomic disadvantage, race/ethnicity, sex, and marital status may influence presentation, surgical complexity, local recurrence (LR), and overall survival (OS).
Aims
The aim of this work is to examine the influence of socioeconomic and demographic factors on the presentation and outcomes of upper extremity soft tissue sarcomas.
Methods and Results
We identified patients treated surgically for primary UE STS (2012-2022). Demographics, tumor characteristics, and outcomes were recorded. Associations between demographics and time to presentation, skin grafting, amputation, and LR were assessed using chi-square and t-tests. Competing risks regression analyzed 3- and 5-year LR, and Kaplan-Meier analysis assessed 5-year OS. Among 181 patients, the mean time to presentation was 17.1 months (SD 34.3), mean tumor size was 7.8 cm (SD 5.7) while 56% required re-excision, 15% underwent amputation, 15% required skin grafting, and 24% experienced LR. Hispanic/Latino patients presented with larger tumor sizes (9.17 ± 5.71 cm vs. 7.43 ± 5.61 cm, p = 0.037). Non-married patients had higher odds of amputation (OR 3.15, p = 0.012), and female sex predicted greater LR risk (OR 2.17, p = 0.037). Twenty-one patients (11.1%) died within five years. In multivariable analysis, increasing tumor size (OR = 1.08; p = 0.010) and high tumor grade (OR = 8.28; p = 0.038) significantly impacted 5-year OS.
Conclusion
While disparities across patient demographics may exist for surgical outcomes for UE STS, racial disparities in overall survival may be mitigated with treatment at an urban, tertiary care sarcoma center.
背景：上肢软组织肉瘤（STS）并不常见，需要复杂的手术治疗。社会经济劣势、种族/民族、性别和婚姻状况可能影响临床表现、手术复杂性、局部复发（LR）和总生存率（OS）。目的：这项工作的目的是检查社会经济和人口因素对上肢软组织肉瘤的表现和结局的影响。方法和结果：我们确定了手术治疗原发性UE STS的患者（2012-2022）。记录人口统计学、肿瘤特征和结果。使用卡方检验和t检验评估人口统计学与就诊时间、植皮、截肢和LR之间的关系。竞争风险回归分析3年和5年LR， Kaplan-Meier分析评估5年OS。在181例患者中，平均出现时间为17.1个月（SD 34.3），平均肿瘤大小为7.8 cm (SD 5.7)， 56%需要再次切除，15%需要截肢，15%需要植皮，24%经历了LR。西班牙裔/拉丁裔患者肿瘤大小较大（9.17±5.71 cm vs. 7.43±5.61 cm, p = 0.037）。未婚患者截肢几率较高（OR 3.15, p = 0.012），女性患者LR风险较高（OR 2.17, p = 0.037）。5年内死亡21例（11.1%）。在多变量分析中，增大肿瘤大小（OR = 1.08; p = 0.010）和高肿瘤分级（OR = 8.28; p = 0.038）显著影响5年OS。结论：虽然UE STS的手术结果可能存在患者人口统计学差异，但在城市三级护理肉瘤中心进行治疗可以减轻总生存率的种族差异。
{"title":"How Do Patient Demographics and Socioeconomic Disadvantage Impact Clinical Presentation, Surgical Outcomes, and Survival for Upper Extremity Soft Tissue Sarcoma?","authors":"Nicole J. Newman-Hung, Kameel Khabaz, Michaela Juels, Giovanni Gamalong, Daniel Chiou, Bailey Mooney, Nicholas M. Bernthal, Lauren E. Wessel","doi":"10.1002/cnr2.70445","DOIUrl":"10.1002/cnr2.70445","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Soft tissue sarcomas (STS) of the upper extremity (UE) are uncommon and may require complex surgical management. Socioeconomic disadvantage, race/ethnicity, sex, and marital status may influence presentation, surgical complexity, local recurrence (LR), and overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this work is to examine the influence of socioeconomic and demographic factors on the presentation and outcomes of upper extremity soft tissue sarcomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We identified patients treated surgically for primary UE STS (2012-2022). Demographics, tumor characteristics, and outcomes were recorded. Associations between demographics and time to presentation, skin grafting, amputation, and LR were assessed using chi-square and <i>t</i>-tests. Competing risks regression analyzed 3- and 5-year LR, and Kaplan-Meier analysis assessed 5-year OS. Among 181 patients, the mean time to presentation was 17.1 months (SD 34.3), mean tumor size was 7.8 cm (SD 5.7) while 56% required re-excision, 15% underwent amputation, 15% required skin grafting, and 24% experienced LR. Hispanic/Latino patients presented with larger tumor sizes (9.17 ± 5.71 cm vs. 7.43 ± 5.61 cm, <i>p</i> = 0.037). Non-married patients had higher odds of amputation (OR 3.15, <i>p</i> = 0.012), and female sex predicted greater LR risk (OR 2.17, <i>p</i> = 0.037). Twenty-one patients (11.1%) died within five years. In multivariable analysis, increasing tumor size (OR = 1.08; <i>p</i> = 0.010) and high tumor grade (OR = 8.28; <i>p</i> = 0.038) significantly impacted 5-year OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While disparities across patient demographics may exist for surgical outcomes for UE STS, racial disparities in overall survival may be mitigated with treatment at an urban, tertiary care sarcoma center.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div> <section> <h3> Background</h3> <p>Adenoid cystic carcinoma (ACC) of the breast is a special subtype of breast cancer.</p> </section> <section> <h3> Aims</h3> <p>This study aimed to systematically characterize the clinicopathologic features, treatment patterns, and prognostic indicators of breast ACC, with the overarching goal of enhancing clinical understanding and optimizing management strategies for this rare malignancy.</p> </section> <section> <h3> Methods and Results</h3> <p>We conducted a retrospective investigation of 22 patients with breast ACC treated at The West China Hospital of Sichuan University between March 2009 and January 2021. Clinical manifestations, therapy strategies, pathological characteristics, and follow-up information were systematically observed and analyzed. This study retrospectively analyzed 22 female patients with breast ACC, with ages ranging from 31 to 75 years. Notably, 54.5% (12/22) of the patients were postmenopausal. A palpable breast mass was the most common initial presenting symptom, observed in 95.5% (21/22) of cases. In terms of molecular subtype, triple-negative breast cancer (TNBC) was identified in 77.3% (17/22) of patients. Conversely, the remaining 22.7% (5/22) of cases showed positive expression for estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2). All patients received surgical treatment, which included simple mastectomy, breast-conserving surgery (BCS), or modified radical mastectomy. The surgical procedures were optionally accompanied by axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). The majority of patients, 90.9% (20/22), were diagnosed at early stages (Stage I or II), while only 2 patients were in Stage III. For postoperative adjuvant therapy, 6 patients underwent radiotherapy, 16 received chemotherapy, 2 received hormonal modulation, and 1 advanced-stage patient participated in a clinical trial with bevacizumab therapy. During the follow-up period, 4 patients (19%) developed distant metastasis. The 5-year disease-free survival rate was 95.4%, with 21 out of 22 patients remaining free from disease recurrence. Remarkably, all patients survived until the end of the last follow-up, suggesting a relatively good prognosis for breast ACC in this cohort.</p> </section> <section> <h3> Conclusion</h3> <p>Breast ACC is a rare type of TNBC that reportedly has indolent biologic behavior. Definitive preoperative diagnosis remains challenging using imaging modalities alone, as conclusive identification relies heavily on h
{"title":"Adenoid Cystic Carcinoma of the Breast: Clinicopathological Features, Therapy Strategy, and Prognosis","authors":"Lan Chen, Shuang Dai, Xi Yan","doi":"10.1002/cnr2.70442","DOIUrl":"10.1002/cnr2.70442","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adenoid cystic carcinoma (ACC) of the breast is a special subtype of breast cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to systematically characterize the clinicopathologic features, treatment patterns, and prognostic indicators of breast ACC, with the overarching goal of enhancing clinical understanding and optimizing management strategies for this rare malignancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We conducted a retrospective investigation of 22 patients with breast ACC treated at The West China Hospital of Sichuan University between March 2009 and January 2021. Clinical manifestations, therapy strategies, pathological characteristics, and follow-up information were systematically observed and analyzed. This study retrospectively analyzed 22 female patients with breast ACC, with ages ranging from 31 to 75 years. Notably, 54.5% (12/22) of the patients were postmenopausal. A palpable breast mass was the most common initial presenting symptom, observed in 95.5% (21/22) of cases. In terms of molecular subtype, triple-negative breast cancer (TNBC) was identified in 77.3% (17/22) of patients. Conversely, the remaining 22.7% (5/22) of cases showed positive expression for estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2). All patients received surgical treatment, which included simple mastectomy, breast-conserving surgery (BCS), or modified radical mastectomy. The surgical procedures were optionally accompanied by axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). The majority of patients, 90.9% (20/22), were diagnosed at early stages (Stage I or II), while only 2 patients were in Stage III. For postoperative adjuvant therapy, 6 patients underwent radiotherapy, 16 received chemotherapy, 2 received hormonal modulation, and 1 advanced-stage patient participated in a clinical trial with bevacizumab therapy. During the follow-up period, 4 patients (19%) developed distant metastasis. The 5-year disease-free survival rate was 95.4%, with 21 out of 22 patients remaining free from disease recurrence. Remarkably, all patients survived until the end of the last follow-up, suggesting a relatively good prognosis for breast ACC in this cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Breast ACC is a rare type of TNBC that reportedly has indolent biologic behavior. Definitive preoperative diagnosis remains challenging using imaging modalities alone, as conclusive identification relies heavily on h","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12805042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunjian Song, Jiayue Li, Meiyue Zhu, Yi Xia, Deqiang Wang, Zhenhua Sun, Liang Ou, Lei Yang
Background
Breast cancer exhibits profound molecular heterogeneity. Each subtype is characterized by distinct biological features, therapeutic responses, and prognostic outcomes. However, a unifying feature across most breast cancer subtypes is an adipocyte-enriched microenvironment. Dysregulated lipid metabolism drives tumor progression across subtypes.
Aims
We developed a universal prognostic model independent of molecular classification based on fatty acid metabolism-related genes.
Methods
Prognostic fatty acid metabolism-related genes were identified in the training set using univariate Cox regression. LASSO regression refined these genes to construct the fatty acid metabolic signature for prognosis (FAMOUS), enabling risk stratification. FAMOUS's prognostic utility was validated in the testing set and external cohort, and across molecular subtypes and therapies.
Results
FAMOUS comprises 15 genes. High FAMOUS scores independently predicted poor overall survival in the training set (HR = 4.97, 95% CI: 3.17–7.79; p < 0.001), testing set (HR = 7.39, 95% CI: 2.19–24.97; p = 0.001), and GSE72245 (HR = 7.97, 95% CI: 3.39–18.75; p < 0.001), after adjusting for molecular subtype, stage, and age. It stratified risk across Luminal A, Luminal B, HER2+, and TNBC subtypes and retained prognostic value in patients receiving chemotherapy, radiotherapy, endocrine therapy, or trastuzumab. High FAMOUS scores correlated with immune-suppressive microenvironments, marked by downregulated immune-related pathways and altered immune cell infiltration (e.g., reduced CD8+ T cells, enriched M2 macrophages), suggesting implications for immunotherapy patient stratification.
Conclusion
FAMOUS is a novel, pan-subtype prognostic tool for breast cancer, transcending molecular classification and therapeutic modalities.
{"title":"A Pan-Subtype Fatty Acid Metabolic Signature Reveals Universal Prognostic Stratification in Breast Cancer","authors":"Yunjian Song, Jiayue Li, Meiyue Zhu, Yi Xia, Deqiang Wang, Zhenhua Sun, Liang Ou, Lei Yang","doi":"10.1002/cnr2.70427","DOIUrl":"10.1002/cnr2.70427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer exhibits profound molecular heterogeneity. Each subtype is characterized by distinct biological features, therapeutic responses, and prognostic outcomes. However, a unifying feature across most breast cancer subtypes is an adipocyte-enriched microenvironment. Dysregulated lipid metabolism drives tumor progression across subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We developed a universal prognostic model independent of molecular classification based on fatty acid metabolism-related genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prognostic fatty acid metabolism-related genes were identified in the training set using univariate Cox regression. LASSO regression refined these genes to construct the fatty acid metabolic signature for prognosis (FAMOUS), enabling risk stratification. FAMOUS's prognostic utility was validated in the testing set and external cohort, and across molecular subtypes and therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FAMOUS comprises 15 genes. High FAMOUS scores independently predicted poor overall survival in the training set (HR = 4.97, 95% CI: 3.17–7.79; <i>p</i> < 0.001), testing set (HR = 7.39, 95% CI: 2.19–24.97; <i>p</i> = 0.001), and GSE72245 (HR = 7.97, 95% CI: 3.39–18.75; <i>p</i> < 0.001), after adjusting for molecular subtype, stage, and age. It stratified risk across Luminal A, Luminal B, HER2+, and TNBC subtypes and retained prognostic value in patients receiving chemotherapy, radiotherapy, endocrine therapy, or trastuzumab. High FAMOUS scores correlated with immune-suppressive microenvironments, marked by downregulated immune-related pathways and altered immune cell infiltration (e.g., reduced CD8+ T cells, enriched M2 macrophages), suggesting implications for immunotherapy patient stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FAMOUS is a novel, pan-subtype prognostic tool for breast cancer, transcending molecular classification and therapeutic modalities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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