Dominika Łubik-Lejawka, I. Gabriel, Adrianna Marzec, Anita Olejek
The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments on the ovarian reserve with a thorough explanation of oncologic treatments’ effects and modes of oncofertility procedures. The aim of this review is to help clinicians in making an informed decision about post-treatment fertility in their patients. Ultimately, it may lead to improved overall long-term outcomes among young populations suffering from cancer.
{"title":"Oncofertility as an Essential Part of Comprehensive Cancer Treatment in Patients of Reproductive Age, Adolescents and Children","authors":"Dominika Łubik-Lejawka, I. Gabriel, Adrianna Marzec, Anita Olejek","doi":"10.3390/cancers16101858","DOIUrl":"https://doi.org/10.3390/cancers16101858","url":null,"abstract":"The number of children, adolescents and young adults diagnosed with cancer has been rising recently. Various oncological treatments have a detrimental effect on female fertility, and childbearing becomes a major issue during surveillance after recovery. This review discusses the impact of oncological treatments on the ovarian reserve with a thorough explanation of oncologic treatments’ effects and modes of oncofertility procedures. The aim of this review is to help clinicians in making an informed decision about post-treatment fertility in their patients. Ultimately, it may lead to improved overall long-term outcomes among young populations suffering from cancer.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140983265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purushothaman Natarajan, G. Delanerolle, Lucy Dobson, Cong Xu, Yutian Zeng, Xuan Yu, Kathleen Marston, Thuan Phan, Fiona Choi, Vanya Barzilova, S. Powell, James Wyatt, Sian Taylor, Jian Qing Shi, D. Hapangama
Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995–31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17–0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17–0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04–6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes.
{"title":"Surgical Treatment for Endometrial Cancer, Hysterectomy Performed via Minimally Invasive Routes Compared with Open Surgery: A Systematic Review and Network Meta-Analysis","authors":"Purushothaman Natarajan, G. Delanerolle, Lucy Dobson, Cong Xu, Yutian Zeng, Xuan Yu, Kathleen Marston, Thuan Phan, Fiona Choi, Vanya Barzilova, S. Powell, James Wyatt, Sian Taylor, Jian Qing Shi, D. Hapangama","doi":"10.3390/cancers16101860","DOIUrl":"https://doi.org/10.3390/cancers16101860","url":null,"abstract":"Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995–31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17–0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17–0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04–6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roger Wilson, Denise Reinke, G. van Oortmerssen, O. Gonzato, Gabriele Ott, Chandrajit P Raut, B. Guadagnolo, Rick L. M. Haas, Jonathan Trent, Robin L. Jones, Lauren Pretorius, Brandi Felser, Mandy Basson, K. Schuster, Bernd Kasper
The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.
{"title":"What Is a Sarcoma ‘Specialist Center’? Multidisciplinary Research Finds an Answer","authors":"Roger Wilson, Denise Reinke, G. van Oortmerssen, O. Gonzato, Gabriele Ott, Chandrajit P Raut, B. Guadagnolo, Rick L. M. Haas, Jonathan Trent, Robin L. Jones, Lauren Pretorius, Brandi Felser, Mandy Basson, K. Schuster, Bernd Kasper","doi":"10.3390/cancers16101857","DOIUrl":"https://doi.org/10.3390/cancers16101857","url":null,"abstract":"The management of sarcomas in specialist centers delivers significant benefits. In much of the world, specialists are not available, and the development of expertise is identified as a major need. However, the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary Principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140983554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available.
{"title":"Novel Endocrine Therapeutic Opportunities for Estrogen Receptor-Positive Ovarian Cancer—What Can We Learn from Breast Cancer?","authors":"Tine Ottenbourgs, E. Van Nieuwenhuysen","doi":"10.3390/cancers16101862","DOIUrl":"https://doi.org/10.3390/cancers16101862","url":null,"abstract":"Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xavier S. Bittman-Soto, Evelyn S. Thomas, Madeline E. Ganshert, Laura L. Mendez‐Santacruz, J. C. Harrell
Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development.
{"title":"The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research","authors":"Xavier S. Bittman-Soto, Evelyn S. Thomas, Madeline E. Ganshert, Laura L. Mendez‐Santacruz, J. C. Harrell","doi":"10.3390/cancers16101859","DOIUrl":"https://doi.org/10.3390/cancers16101859","url":null,"abstract":"Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julian Mehl, D. Akhoundova, Ulrike Bacher, B. Jeker, Gaëlle Rhyner Agocs, A. Ruefer, Susanne Soltermann, Martin Soekler, Annette Winkler, M. Daskalakis, Thomas Pabst
Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.
{"title":"Daratumumab during Myeloma Induction Therapy Is Associated with Impaired Stem Cell Mobilization and Prolonged Post-Transplant Hematologic Recovery","authors":"Julian Mehl, D. Akhoundova, Ulrike Bacher, B. Jeker, Gaëlle Rhyner Agocs, A. Ruefer, Susanne Soltermann, Martin Soekler, Annette Winkler, M. Daskalakis, Thomas Pabst","doi":"10.3390/cancers16101854","DOIUrl":"https://doi.org/10.3390/cancers16101854","url":null,"abstract":"Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140985117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aakash Desai, Alexander Xiao, Daheui Choi, M. D. Toruner, Daniel J. Walden, T. Halfdanarson, Steven R Alberts, Robert R. McWilliams, Amit Mahipal, Daniel H Ahn, Hani Babiker, Gulnaz Stybayeva, Alexander Revzin, S. Kizilbash, Alex Adjei, Tanios B. Bekaii-Saab, A. S. Mansfield, Ryan M. Carr, Wen Wee Ma
Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.
{"title":"Molecular Characterization and Therapeutic Opportunities in KRAS Wildtype Pancreatic Ductal Adenocarcinoma","authors":"Aakash Desai, Alexander Xiao, Daheui Choi, M. D. Toruner, Daniel J. Walden, T. Halfdanarson, Steven R Alberts, Robert R. McWilliams, Amit Mahipal, Daniel H Ahn, Hani Babiker, Gulnaz Stybayeva, Alexander Revzin, S. Kizilbash, Alex Adjei, Tanios B. Bekaii-Saab, A. S. Mansfield, Ryan M. Carr, Wen Wee Ma","doi":"10.3390/cancers16101861","DOIUrl":"https://doi.org/10.3390/cancers16101861","url":null,"abstract":"Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140984480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric Ovruchesky, Elizabeth Pan, Melis Guer, Andrew Elliott, Shankar Siva, P. Ravi, B. McGregor, Aditya Bagrodia, I. Derweesh, Pedro C Barata, Elisabeth I Heath, Emmanuel S. Antonarakis, S. Darabi, Dave S. B. Hoon, Amir Mortazavi, Toni K. Choueiri, C. Nabhan, Shuanzeng Wei, Rana R McKay
Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93, p < 0.05). Conclusions: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.
{"title":"Characterization of FOLH1 Expression in Renal Cell Carcinoma","authors":"Eric Ovruchesky, Elizabeth Pan, Melis Guer, Andrew Elliott, Shankar Siva, P. Ravi, B. McGregor, Aditya Bagrodia, I. Derweesh, Pedro C Barata, Elisabeth I Heath, Emmanuel S. Antonarakis, S. Darabi, Dave S. B. Hoon, Amir Mortazavi, Toni K. Choueiri, C. Nabhan, Shuanzeng Wei, Rana R McKay","doi":"10.3390/cancers16101855","DOIUrl":"https://doi.org/10.3390/cancers16101855","url":null,"abstract":"Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93, p < 0.05). Conclusions: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140983220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satoshi Seno, K. Iwashita, Akifumi Kajiwara, Rie Sasaki, Tatsuya Furukawa, M. Teshima, H. Shinomiya, Naomi Kiyota, Rod Lynch, Kenji Yoshida, T. Ishihara, D. Miyawaki, K. Nibu, Ryohei Sasaki
Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.
{"title":"Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1–T2 Squamous Cell Carcinoma of the Glottic Larynx","authors":"Satoshi Seno, K. Iwashita, Akifumi Kajiwara, Rie Sasaki, Tatsuya Furukawa, M. Teshima, H. Shinomiya, Naomi Kiyota, Rod Lynch, Kenji Yoshida, T. Ishihara, D. Miyawaki, K. Nibu, Ryohei Sasaki","doi":"10.3390/cancers16101850","DOIUrl":"https://doi.org/10.3390/cancers16101850","url":null,"abstract":"Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140986807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastian Staebler, Sebastian Hoechst, Aranya Thongmao, Nadja Schneider, Anja K. Bosserhoff, S. Kuphal
Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.
{"title":"The Role of T-Cadherin (CDH13) in Treatment Options with Garcinol in Melanoma","authors":"Sebastian Staebler, Sebastian Hoechst, Aranya Thongmao, Nadja Schneider, Anja K. Bosserhoff, S. Kuphal","doi":"10.3390/cancers16101853","DOIUrl":"https://doi.org/10.3390/cancers16101853","url":null,"abstract":"Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.","PeriodicalId":504676,"journal":{"name":"Cancers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140987239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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