Anti-Cancer Drugs最新文献

As epidermal growth factor receptor ( EGFR ) exon 20 insertion mutations generally result in poor sensitivity to EGFR -tyrosine kinase inhibitors (TKIs), the administration of EGFR -TKIs is not recommended in non-small-cell lung cancer (NSCLC). Nonetheless, EGFR exon 20 A763_Y763insFQEA, a genotype of EGFR exon 20 insertion mutations, has some sensitivity to EGFR -TKIs. However, the therapeutic effects of EGFR -TKIs alone for EGFR exon 20 A763_Y763insFQEA are insufficient compared to those for common EGFR mutations. Therefore, more effective treatment options are required for this mutation. Herein, we present a case in which treatment with erlotinib plus ramucirumab led to a complete response and progression-free survival of 13 months in a 79-year-old man with advanced NSCLC harboring EGFR exon 20 A763_Y763insFQEA. This case suggests that this regimen should be considered as an effective treatment option for such patients.

Tafasitamab, an anti-CD19 mAb, has demonstrated promising efficacy in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in Western populations, but its use in Chinese patients has not been reported. This case series reports the use of tafasitamab in four Chinese patients with R/R DLBCL. Four patients with R/R DLBCL were treated at the Department of Hematology, Hainan Hospital of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. All patients had previously received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. After treatment with tafasitamab and lenalidomide, two patients with primary refractory disease, one achieved a partial response and another had stable disease. One patient who relapsed after autologous stem-cell transplantation received tafasitamab plus lenalidomide and a Bruton tyrosine kinase (BTK) inhibitor and showed remarkable tumor reduction in all sites except for the lymph nodes in the left inguinal region. One patient who relapsed after second-line therapy achieved complete remission with tafasitamab monotherapy. Tafasitamab-based treatment was well-tolerated, with the most common adverse event being neutropenia. Our real-world experience first suggests that tafasitamab-based flexible treatment may be a potential treatment option for Chinese patients with R/R DLBCL, supporting the need for further investigation into its efficacy and safety in Chinese patients, with a particular focus on exploring directions such as combinations with BTK inhibitors.

Chemotherapy improves outcomes in patients with high-risk early or locally advanced breast cancer, but older adults often experience higher toxicity that leads to treatment delays, dose reductions, and reduced relative dose intensity (RDI). This study examined predictors of low RDI and its impact on overall survival (OS) in women aged over 65 years treated with neoadjuvant or adjuvant chemotherapy at San Juan de Dios Hospital (Costa Rica) between November 2018 and April 2023. A total of 264 patients (mean age: 70.1 years) were included. Nearly one-third had a Charlson Comorbidity Index (CMI) greater than 6. Tumor subtypes were hormone receptor (HR)+/ human epidermal growth factor receptor (HER2)-(48.9%), HR+/HER2+ (15.9%), HR-/HER2+ (33%), and triple-negative (17.8%). Most patients (68.6%) received anthracycline-based regimens. Overall, 17.4% had an RDI below 80%. After a median follow-up of 54.6 months, 56 deaths were recorded. Low RDI was significantly associated with worse OS [hazard ratio: 1.79, 95% confidence interval (CI): 1.02-3.13; P = 0.04]. Independent predictors of low RDI were anthracycline-based therapy [odds ratio (OR): 4.76, 95% CI: 2.17-9.09], CMI greater than 6 (OR: 2.13, 95% CI: 1.02-4.54), and age more than 70 years (OR: 2.38, 95% CI: 1.14-5.01). These findings suggest that advanced age, comorbidities, and anthracycline regimens increase the risk of reduced RDI, which negatively impacts survival. Supportive measures are critical to maintain chemotherapy intensity in older women.

Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy that frequently overexpresses Human Epidermal Growth Factor Receptor 2 (HER2). Despite the increasing recognition of HER2-targeted strategies, evidence remains limited and largely derived from small trials and case series. We report the case of a middle-aged man with HER2-positive metastatic SDC who achieved near-complete pathologic and radiological response to trastuzumab and docetaxel, enabling surgical resection for locoregional control. This case highlights the role of anti-HER2 therapy as a first-line strategy in SDC and underscores the importance of individualized management plans integrating systemic treatment and locoregional measures.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy represent the standard of care for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). While clinical trials established their efficacy, real-world evidence on safety, dose adjustments, and outcomes remains limited. We conducted a prospective observational study including patients with HR+/HER2- mBC treated with palbociclib, ribociclib, or abemaciclib across three oncology units between 2019 and 2024. Data on adverse events, dose modifications, progression-free survival (PFS), and overall survival (OS) were collected and analyzed. Adverse events were reported in 77.5% of patients. Neutropenia was the most frequent adverse event with palbociclib and ribociclib, while diarrhea and hepatic toxicity predominated with abemaciclib. Pulmonary toxicity occurred in 19.1% of abemaciclib-treated patients, often in those previously irradiated. Median PFS and OS were 26.4 and 31.1 months, respectively. The occurrence of grade 3-4 adverse events correlated with improved OS (37.1 vs. 23.0 months, P  < 0.001). Dose reductions, required in more than 60% of patients, did not compromise efficacy; instead, they were associated with longer PFS and OS. Conversely, treatment discontinuation predicted worse outcomes. In real-world practice, CDK4/6i toxicities are frequent but manageable. Proactive toxicity management and timely dose adjustments are essential to sustain treatment benefit. Dose reductions may even improve outcomes, underscoring the value of individualized dosing strategies.

Scirrhous gastric cancer (SGC), including the Borrmann type IV subtype, is characterized by a desmoplastic stroma, rapid progression, and a poor prognosis with limited effective treatment options. While fibroblast growth factor receptor 2 (FGFR2) alterations are recognized therapeutic targets in some cancers, their clinical application in gastric cancer, particularly in SGC, remains underexplored. We present the case of a 47-year-old female with advanced, chemotherapy-refractory Borrmann type IV gastric cancer harboring FGFR2 rearrangement and amplification. Treatment with the selective FGFR1-3 inhibitor pemigatinib elicited a marked clinical and serological response; however, disease progression ensued after 3 months. Comprehensive genomic profiling revealed an acquired FGFR2 N549K mutation, a recognized on-target resistance mechanism. Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.

Advanced hepatocellular carcinoma (HCC) with extensive metastases is associated with a poor prognosis, highlighting the need for individualized, multimodal treatment strategies. We present the case of a 54-year-old male with advanced HCC (cT3NxM1, Child-Pugh B) and spinal as well as bilateral pulmonary metastases who experienced disease progression after multiple lines of therapy. A dynamically adjusted, multidisciplinary regimen was implemented, incorporating transarterial chemoembolization (TACE), surgery, immunotherapy, and targeted therapy. The final regimen - combining nivolumab plus ipilimumab (O+Y) with TACE and lenvatinib - achieved a partial response in lung metastases, with a progression-free survival exceeding one year and overall survival of over 24 months. This case underscores the therapeutic potential of O+Y in later-line settings and demonstrates the clinical value of an integrated, personalized treatment paradigm for advanced HCC.

Dysregulated expression of mitochondrial creatine kinase 1B (CKMT1B), a member of the creatine kinase family, has been linked to tumor progression. However, its specific function in lung adenocarcinoma (LUAD) remains unclear. Bioinformatics analyses were performed to evaluate CKMT1B and its upstream transcription factor PITX2 in LUAD. CKMT1B and PITX2 expression levels were determined by quantitative PCR. The functional impact on cell stemness was subsequently evaluated using CCK-8, sphere formation assay, flow cytometry, and western blot. CKMT1B-mediated lipid accumulation was examined via BODIPY staining and measurements of triglyceride and glycerol concentration. The PITX2-CKMT1B interaction was validated through dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays, with the regulatory mechanism further substantiated by functional rescue experiments. CKMT1B was upregulated in LUAD and linked with poor prognosis. Its knockdown suppressed cell proliferation, sphere-forming capacity, and stemness-related protein expression (CD133, Bmi-1, SOX-2). Furthermore, CKMT1B overexpression facilitated lipid accumulation and stemness, effects that were reversible by the lipase inhibitor Orlistat. Mechanistically, PITX2 was identified as an upstream transcription factor of CKMT1B. PITX2 expression was positively correlated with CKMT1B, and high PITX2 expression predicted poor outcomes. In functional rescue experiments, PITX2 knockdown significantly reduced lipid accumulation and stemness, while these effects were partially restored by CKMT1B overexpression. PITX2 promotes lipid accumulation and enhances stemness in LUAD cells by transcriptionally activating CKMT1B, suggesting the PITX2/CKMT1B axis as a potential therapeutic target for LUAD treatment.

Neurotoxicity is one of the major complications in cancer patients following paclitaxel-containing regimens. Matricaria chamomilla L., isolated from the German chamomile, has anti-inflammatory and antioxidant features. In this study we evaluated the preventive impact of a chamomile oral formulation against paclitaxel-induced neurotoxicity in cancer patients. In this triple-blind clinical trial, cancer patients on paclitaxel were randomly allocated to chamomile oral solution (n = 40), or the placebo (n = 40) 5 ml three times a day for four courses of chemotherapy starting one day before the paclitaxel injection. At the end of each chemotherapy course, patients in both groups were evaluated and graded according to CTCAE (Common Terminology Criteria for Adverse Events). Also, anxiety and sleep disorder were evaluated at the beginning and end of the study based on Generalized Anxiety Disorder-7 and Pittsburgh Sleep Quality Index criteria, respectively. At the end of the four cycles of chemotherapy, there was no significant difference between the two groups in terms of the neuropathy CTCAE score. In terms of the various components of the sleep questionnaire, only the individual's overall description of sleep quality at the end of the study was significantly better in the treatment group (P = 0.026). Sleep quality was also significantly better (P = 0.027), and the chance of good sleep quality in the intervention group was 4.48 times higher. Regarding the anxiety score, despite a significant decrease in both groups, the difference between the two groups at the end of the fourth course was not significant. Neither group experienced any adverse effects. Although chamomile oral solution did not significantly lessen neuropathy, findings propose that it may significantly ameliorate sleep quality in patients receiving chemotherapy as a low-cost, low-risk treatment. It also has no significant impact on reducing the level of anxiety in cancer patients.

Isovanillin, a natural coumarin compound, exhibits biological functions; however, its anti-gastric cancer process is not well understood. This research examined the pathway underlying isovanillin's effects on gastric cancer cells. Cell viability assays demonstrated that isovanillin effectively reduced the viability of various gastric cancer cell lines. Network pharmacological analysis identified 41 key targets implicated in isovanillin's anti-gastric cancer activity, highlighting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) pathways as critical components. Apoptosis assays revealed that isovanillin promoted apoptosis by upregulating the manifestation of p-p38 and p-JNK and suppressing p-ERK and p-STAT3. Cellular cycle examination revealed that isovanillin triggered G2/M stage block via the suppression of p-PI3K, p-AKT, cell cycle regulators 1/2 (CDK1/2), and cyclin B1, and the increase of cell cycle inhibitor 1A (p21) and cell cycle inhibitor 1B (p27). Cell metastasis assays showed that isovanillin suppressed the migration of MKN-45 cells through diminishing the concentrations of p-PI3K, p-AKT, N-cadherin, matrix metalloproteinase-2, as well as matrix metalloproteinase-9, while increasing E-cadherin expression. Furthermore, isovanillin exerted its anti-gastric cancer effects by promoting ROS accumulation, thereby modulating associated signaling pathways. The ROS scavenger N-acetyl-l-cysteine reversed isovanillin-induced protein expression changes. In conclusion, isovanillin induces apoptosis, G2/M phase arrest, and inhibits MKN-45 cell migration by mediating ROS to regulate the MAPK and PI3K signaling pathways.