Search Results (246)

Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed nations, exhibiting significant molecular heterogeneity that impacts prognosis and treatment response, particularly in advanced or recurrent settings. Traditional classification is increasingly supplemented by molecular subtyping (POLE-ultramutated, MSI-high/dMMR, NSMP, p53-mutated/CNH), which provides crucial prognostic information and predicts benefit from immunotherapy. This review summarizes the landscape of predictive biomarkers for immune checkpoint inhibitor (ICI) therapy in EC, emphasizing a new therapeutic scenario for advanced and recurrent EC. Mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), leading to high tumor mutational burden (TMB) and increased neoantigen production, is the most established predictor, resulting in FDA approvals for pembrolizumab and dostarlimab in this subgroup. POLE mutations also confer hypermutation and high immunogenicity, predicting a favorable ICI response. Other biomarkers, including PD-L1 expression and TMB, show variable correlation with response and require further standardization. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs), also influences treatment outcomes. Clinical trials have demonstrated significant survival benefits for ICIs combined with chemotherapy (e.g., dostarlimab/pembrolizumab + carboplatin/paclitaxel) in first-line settings, especially for dMMR/MSI-H EC, and for ICI combinations with targeted agents (e.g., lenvatinib + pembrolizumab) in previously treated patients. Integrating molecular classification and validated biomarkers is essential for optimizing patient selection and developing personalized immunotherapy strategies for EC. Full article

Purpose: This exploratory retrospective analysis examined racial disparities in fall-related injuries among Black and White breast cancer survivors who received chemotherapy, focusing on the risks associated with specific chemotherapy regimens. Methods: Using real-world data from the TriNetX research platform, we analyzed a cohort of 3223 Stage I–III breast cancer survivors with complete data on race, chemotherapy exposure, and fall-related injuries. The final sample included only Black and White patients treated with chemotherapy between 1 January 2019 and 31 December 2023. Fall events within six months post-chemotherapy were analyzed. Logistic regression models evaluated associations between chemotherapy type and fall risk by race. Results: Black breast cancer survivors experienced a significantly higher rate of fall-related injuries (14.7%) compared to White survivors (10.0%) (p < 0.001). The risk was especially elevated among Black patients receiving Cyclophosphamide, Docetaxel, and Carboplatin. Conclusion: This study highlights racial differences in chemotherapy-associated fall risk. While the findings are observational and limited by data availability, they underscore the need for more inclusive survivorship care and further investigation using detailed clinical and contextual variables. Real-world platforms like TriNetX can help identify early signals of disparities that merit prospective study. Full article

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of cancer treatment, which is more common in patients with ovarian cancer who are receiving paclitaxel and carboplatin treatment. Although prior studies have explored the association between obesity and CIPN, most relied on subjective grading systems. This study aims to evaluate the relationship between being overweight and CIPN using the Total Neuropathy Score (TNS), a more objective and comprehensive assessment tool. The purpose of this study is to investigate the relationship between being overweight and the onset and severity of CIPN in a cohort of South Korean patients with ovarian cancer who were treated with paclitaxel and carboplatin. Methods: The study was conducted retrospectively at a single tertiary hospital in South Korea from March 2013 to February 2022. Included in this study were forty-two individuals who were diagnosed with epithelial ovarian cancer and who had developed neuropathic symptoms following chemotherapy. Patient characteristics, laboratory findings, and disease-specific TNS were analyzed. Results: Overweight patients showed significantly more severe CIPN, with higher Total Neuropathy Scores (TNS; p = 0.019) and earlier symptom onset (p < 0.05) compared to normal-weight patients. Causal mediation analysis also revealed a significant direct effect of BMI on TNS (p = 0.006). However, no significant correlation was found between BMI and TNS using Kendall’s rank correlation, and other neuropathic symptoms or laboratory parameters did not show statistically significant group differences. Conclusions: The study suggests that overweight may be associated with the severity and onset of CIPN in patients with ovarian cancer who are receiving paclitaxel and carboplatin chemotherapy. While the results are preliminary, they underscore the importance of addressing this modifiable risk factor in clinical care. Further research is needed to better understand the underlying mechanisms and to inform future therapeutic strategies. Full article

Background: The predictive value of muscle-related indicators in triple-negative breast cancer (TNBC) patients undergoing neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the association between the skeletal muscle density (SMD) and clinical variables related to the physical reserve with respect to its impact on the pathologic complete response (pCR). Methods: We retrospectively analyzed TNBC patients who underwent NAC at Seoul St. Mary’s Hospital, Catholic University of Korea, from March 2021 to March 2024, via receiving paclitaxel/carboplatin followed by doxorubicin/cyclophosphamide, with or without pembrolizumab. Muscle indices were assessed from CT measurements of the entire cross-sectional muscle area at the L3 level using commercial deep learning software (ClariMetabo version 1.03). Results: A total of 144 patients were included, where 102 received chemoimmunotherapy (NACIT) and 42 received chemotherapy alone (NACT). A higher SMD was significantly associated with a younger age, lower BMI, and fewer comorbidities. In the NACIT group, patients in the high-SMD group (n = 68) demonstrated a higher relative dose intensity (p = 0.003) and improved pCR rates (63.2% vs. 44.1%, p = 0.066) compared with the low-SMD group (n = 34). The multivariable regression analysis identified a higher SMD (per 5-unit increment: OR = 1.67, p = 0.003) and increased PD-L1 combined positive score (per 10-unit increment: OR = 1.38, p = 0.019) as independent predictors of a pCR. The event-free survival was significantly longer in the high-SMD group (p = 0.017) and among patients that achieved a pCR (p < 0.001). In the NACT group, the SMD was not associated with a pCR or survival. Conclusions: The CT-measured SMD reflected the physical reserve in the TNBC patients that received NAC. Alongside the CPS, SMD may serve as a predictive marker for NACIT efficacy. Full article

Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence despite advancements in treatment. The primary treatment for localized ASCC is radiochemotherapy (RCT), which achieves high rates of tumor regression in most cases, but up to 30% of patients experience recurrence or persistent disease. Salvage surgery, such as an abdominoperineal resection (APR), is often used for recurrent disease but is associated with significant morbidity and limited oncological outcomes. Patients with small T1 tumors may also benefit from primary local excision. For patients with metastatic or unresectable recurrent ASCC, chemotherapy, particularly carboplatin and paclitaxel, remains the standard treatment. New therapeutic strategies, including immune checkpoint inhibitors like pembrolizumab, are showing promise, particularly in PD-L1-positive tumors. Clinical trials have suggested that immunotherapy offers a potential alternative for patients for whom conventional treatments have failed, though the overall response rates remain modest. Re-radiation and intraoperative radiotherapy combined with salvage surgery may improve the outcomes for select patients, though the data are still limited. The management of recurrent or persistent ASCC requires a personalized approach, incorporating both established and emerging therapies to optimize patient outcomes. Further research is needed to refine these treatment strategies. Full article

Background: Glioblastoma multiforme (GBM) is a very malignant brain tumor. GBM exhibits cellular and molecular heterogeneity that can be exploited to improve patient outcomes by individually tailoring chemotherapy regimens. Objective: Our objective was to develop a predictive model of the life expectancy of GBM patients using data on tumor cells’ sensitivity to chemotherapy drugs, as well as the levels of blood cells and proteins forming the tumor microenvironment. Methods: The investigation included 31 GBM patients from the Almazov Medical Research Centre (Saint Petersburg, Russia). The cytotoxic effects of chemotherapy drugs on GBM cells were studied by an MTT test using a 50% inhibitory concentration (IC₅₀). We analyzed the data with life expectancy by a one-way ANOVA, principal component analysis (PCA), ROC, and Kaplan–Meier survival tests using GraphPad Prism and Statistica 10 software. Results: We determined in vitro the IC₅₀ of six chemotherapy drugs for GBM and 32 clinical and biochemical blood indicators for these patients. This model includes an assessment of only three parameters: IC₅₀ of tumor cells to carboplatin (CARB) higher than 4.115 μg/mL, as well as levels of band neutrophils (NEUT-B) below 2.5% and total protein (TP) above 64.5 g/L in the blood analysis, which allows predicting with 83.3% probability (sensitivity) the life expectancy of patients for 15 months or more. In opposite, a change in these parameters—CARB above 4115 μg/mL, NEUT-B below 2.5%, and TP above 64.5 g/L—predict with 83.3% probability (specificity) no survival rate of GBM patients for more than 15 months. The relative risk for CARB was 6.41 (95 CI: 4.37–8.47, p = 0.01); for NEUT-B, the RR was 0.40 (95 CI: 0.26–0.87, p = 0.09); and for TP, it was 2.88 (95 CI: 1.57–4.19, p = 0.09). Overall, the model predicted the risk of developing a positive event (an outcome with a life expectancy more than 10 months) eight times (95 CI 6.34–9.66, p < 0.01). Cross k-means validation on three clusters (n = 10) of the model showed that its average accuracy (sensitivity and specificity) for cluster 1 was 74.98%; for cluster 2, it was 66.7%; and for cluster 3, it was 60.0%. At the same time, the differences between clusters 1, 2, and 3 were not significant. The results of the Sobel test show that there are no interactions between the components of the model, and each component is an independent factor influencing the event (life expectancy, survival) of GBM patients. Conclusions: A simple predictive model for GBM patients’ life expectancy has been developed using statistical analysis methods. Full article

Patients with a BRCA1 germline mutation often represent a challenge for medical healthcare, since they develop malignancies that tend to be more aggressive and which need to be addressed in multidisciplinary teams with more individualized therapies. We report a case of a 37-year-old woman with a BRCA1 mutation who was diagnosed and treated for high-grade papillary serous carcinoma of the fallopian tube. Eight years later, her regular check-up imaging revealed a latero-aortic lymphadenopathy and a right breast tumor. She underwent a fine needle breast biopsy which was positive for invasive non-specific type carcinoma with negative estrogen, progesterone and Her2 receptors in immunohistochemistry tests. The patient underwent debulking surgery for metastatic lymphadenopathy, followed by chemotherapy with Carboplatin and Paclitaxel, and a modified right mastectomy with axillary lymphadenectomy. She subsequently initiated therapy with the PARP inhibitor Olaparib. No evidence of tumor recurrence was detected during the six-month postoperative follow-up period. The primary goal of this paper is to emphasize the complexity and challenges of managing patients with BRCA1 mutations who develop synchronous malignancies. This case report aims to highlight the increasing role of precision medicine and the importance of personalized, multidisciplinary therapeutic strategies, which include surgery, chemotherapy, and targeted therapies. Full article

The cancer chemotherapy regimen of a taxane and platinum combination was developed more than forty years ago, yet remains the cornerstone of treatment for several major cancer types today. Although many new agents targeting cancer genes and pathways have been developed and evaluated, none have been sufficient to replace the long-established taxane/platinum combination. This leads us to ponder why, after four decades of colossal efforts, multiple discoveries, and tremendous advances in understanding gene mutations and biology, the development of conceptually superior targeted therapies has not yet achieved overwhelming success in replacing cytotoxic chemotherapy. The concept of targeted therapy is based on the idea that blocking the altered pathway(s) crucial for cancer development (and maintenance), the disturbance in cellular signaling, metabolism, and functions will make the targeted cancer cells unfit and trigger programmed cell death in cancer cells, but without the significant side effects that limit chemotherapy. We propose that the lack of anticipated triumphs of targeted therapy stems from the desensitization of programmed cell death pathways during neoplastic transformation and malignant progression of cancer cells. This renders the targeting drugs largely ineffective at killing cancer cells and mostly insufficient in clinical implements. Recent advances in understanding suggest that, in contrast to targeted therapies, taxanes and platinum agents kill cancer cells by physical rupturing nuclear membranes rather than triggering apoptosis, making their effect independent of the intrinsic cellular programmed cell death mechanism. This new recognition of the non-programmed cell death mechanism in the success of chemotherapeutic agents, such as taxanes and platinum, may inspire oncologists and cancer researchers to focus their efforts more productively on developing effective non-programmed cell death cancer therapies to replace or significantly improve the application of the current standard taxane/platinum regimens. Full article

Coordination polymers containing zinc and imidazolium-based dicarboxylate ligands, [L^R]⁻, were synthesized by reacting zinc acetate with HL^R compounds, 1. The resulting complexes were characterized and structurally identified using single-crystal X-ray diffraction, revealing polymeric structures for the complexes [Zn(L^R)₂]_n (R = Gly, 2a; βAla, 2b) and [Zn(L^Leu)₂(H₂O)₂]_n (2c). In these structures, the [L^R]⁻ ligands adopt a bridging monodentate μ-κ¹-O¹,κ¹-O³ coordination mode, resulting in distorted tetrahedral (2a, 2b) or octahedral (2c) geometries around the zinc center. When the synthesis was carried out in the presence of amino acids, mixed ligand complexes [Zn(L^R)(aa)(H₂O)]_n (R = aa = Val, 2d, and R = aa = Ile, 2e) were formed. Complexes 2d–2e were also structurally characterized using single-crystal X-ray crystallography, revealing that the ligand [L^R]⁻ maintained the same coordination mode, while the zinc center adopted a five-coordinated geometry. The cytotoxic activity of complexes 2a–2e was evaluated against three cancer cell lines and one non-cancerous cell line. Remarkably, these complexes exhibited higher toxicity against cancer cells than against the non-cancerous cell line, and they showed greater selectivity than carboplatin, a commonly used chemotherapy drug. Although, in general, these complexes did not surpass the selectivity of gemcitabine, complex 2c stood out for exhibiting a selectivity index value similar to that of gemcitabine against melanoma cells. Among the series, compounds 2a–2c demonstrated the highest activity, with 2a being the only complex with some selective activity against lung cancer. Complex 2b was the most active, though with low selectivity, while complex 2c exhibited the highest selectivity for melanoma and bladder cancer (selectivity index of 3.0). Full article

Avelumab first-line maintenance (1LM) is approved for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who do not have disease progression after platinum-based chemotherapy (PBC). This retrospective study describes real-world treatment patterns and clinical outcomes in patients with la/mUC who initiated first-line (1L) systemic treatments, including avelumab 1LM, within iKnowMed, the US community oncology electronic health records database, between 1 December 2019 and 30 November 2023 and followed through 28 February 2024. In total, 1658 patients with la/mUC initiated 1L treatment: immuno-oncology (IO) monotherapy (41.2%), PBC only (32.4%), PBC followed by avelumab 1LM (11.2%), and other treatments (15.1%). The median OS (95% CI) from the start of 1L treatment was 20.4 (13.8, 30.0), 11.0 (8.5, 14.5), and 14.6 (12.6, 17.3) months for cisplatin-based only, carboplatin-based only, and IO monotherapy, respectively. Among the overall population, 36.1% and 11.8% of patients received second-line (2L) and third-line treatment, respectively. The median (95% CI) OS from the start of avelumab 1LM was 18.5 (13.8, 23.8) months. After discontinuation of avelumab 1LM, 43.5% received 2L treatment, and 59.3% of those received enfortumab vedotin (EV); the median (95% CI) OS from start of 2L EV was 12.7 (7.2, 16.5) months. Survival outcomes among patients treated with avelumab 1LM and 2L EV are consistent with respective clinical trials and other real-world studies. Full article

Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood–brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months. However, most patients eventually fail the treatment and progress. This is why we wish to expand our portfolio of options in terms of chemotherapy agents available for IA administration. In this study, we tested topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration in the F98-Fischer glioma-bearing rat model as a screening tool for identifying potential candidate drugs. The topotecan IA group showed increased survival compared to the intravenous (IV) group (29.0 vs. 23.5), whereas the IV cytarabine group survived longer than the IA group (26.5 vs. 22.5). The new formulation of carboplatin showed a significant increase in survival compared to two previous studies with the conventional form (37.5 vs. 26.0 and 30.0). As for paclitaxel, it was too neurotoxic for IA administration. Topotecan and the new formulation of carboplatin demonstrated significant results, warranting their transition for consideration in clinical trials. Full article

BCC is the most prevalent form of skin cancer, characterized by diverse clinical and pathological subtypes ranging from indolent to highly aggressive forms. While the majority of BCC cases are treated effectively with surgery or local therapies, locally advanced BCC (laBCC) and metastatic BCC (mBCC) pose significant therapeutic challenges. Recent advances in HHIs and immunotherapy have transformed the treatment landscape in such cases. However, resistance and intolerance to these treatments necessitate alternative approaches, including chemotherapy. Platinum-based agents such as cisplatin and carboplatin have shown limited efficacy but remain viable options in rapidly progressive cases. Among the therapeutic innovations to be explored, further lines of immunotherapy as well as combination therapies involving immunotherapy and targeted therapy have been proposed. This review synthesizes the current understanding about BCC subtypes, risk stratification, and emerging treatments, with a particular focus on laBCC and mBCC. Full article

The poor prognosis for high-grade serous ovarian cancer (HGSOC), the dominant subtype of ovarian cancer, reflects its aggressive nature, late diagnosis, and the highest mortality rate among all gynaecologic cancers. Apart from late diagnosis, the main reason for the poor prognosis and its unsuccessful treatment is primarily the emergence of chemoresistance to carboplatin. Although there is a good response to primary treatment, the disease recurs in 80% of cases, at which point it is largely resistant to carboplatin. The introduction of novel targeted therapies in the second decade of the 21st century has begun to transform the treatment of HGSOC, although their impact on overall survival remains unsatisfactory. Targeting the specific pathways known to be abnormally activated in HGSOC is especially difficult due to the molecular diversity of its subtypes. Moreover, a range of molecular changes are associated with acquired chemoresistance, e.g., reversion of BRCA1 and BRCA2 germline alleles. In this review, we examine the advantages and disadvantages of approved targeted therapies, including bevacizumab, PARP inhibitors (PARPis), and treatments targeting cells with neurotrophic tyrosine receptor kinase (NTRK), B-rapidly accelerated fibrosarcoma (BRAF), and rearranged during transfection (RET) gene alterations, as well as antibody–drug conjugates. Additionally, we explore promising new targets under investigation in ongoing clinical trials, such as immune checkpoint inhibitors, anti-angiogenic agents, phosphatidylinositol-3-kinase (PI3K) inhibitors, Wee1 kinase inhibitors, and ataxia telangiectasia and Rad3-related protein (ATR) inhibitors for platinum-resistant disease. Despite the development of new targeted therapies, carboplatin remains the fundamental medicine in HGSOC therapy. The correct choice of treatment strategy for better survival of patients with advanced HGSOC should therefore include a prediction of patients’ risks of developing chemoresistance to platinum-based chemotherapy. Moreover, effective targeted therapy requires the selection of patients who are likely to derive clinical benefit while minimizing potential adverse effects, underscoring the essence of precision medicine. Full article

Chemotherapy for cancer frequently uses platinum-based medications, including oxaliplatin, carboplatin, and cisplatin; however, due to their high systemic toxicity, lack of selectivity, drug resistance, and other side effects, platinum-based medications have very limited clinical application. As a first-line medication in antitumor therapy, oxaliplatin must be administered to minimize side effects while achieving anticancer objectives. A new CDC7 inhibitor called XL413 has demonstrated promising antitumor therapeutic effects in a variety of malignant tumors and may have anticancer properties. This offers a fresh viewpoint on how to lessen oxaliplatin resistance and, specifically, increase the potency of already prescribed anticancer therapies. In this paper, the current developments in anticancer therapy are discussed, along with the many mechanisms of oxaliplatin’s antitumor effects, clinical treatment challenges, and related approaches. We conducted more research on oxaliplatin resistance that arose during chemotherapy and searched for ways to lessen it in order to enhance its chemotherapeutic performance. Ultimately, we studied how distinct resistance routes relate to one another. Meanwhile, XL413, a novel CDC7 inhibitor, offers a perspective on the possibilities for developing treatment approaches for this innovation point. The search terms “Oxaliplatin, XL413, drug resistance, cancer treatment,” etc., were applied in the X-MOL and PubMed databases for this review’s literature search. Boolean logic was then employed to maximize the search approach. These databases can offer thorough research data and cover a broad range of biological publications. Excluded publications were works of low relevance, duplicates, or those with insufficient information. The mechanism of oxaliplatin’s anticancer effect, oxaliplatin resistance and its amelioration, and the role of XL413 in oxaliplatin treatment were the main topics of the 140 publications that were ultimately included for analysis. Full article