Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.

Testicular germ-cell tumors (TGCT) have been widely recognized for their outstanding survival rates, commonly attributed to their high sensitivity to cisplatin-based therapies. Despite this, a subset of patients develops cisplatin resistance, for whom additional therapeutic options are unsuccessful, and ~20% of them will die from disease progression at an early age. Several efforts have been made trying to find the molecular bases of cisplatin resistance. However, this phenomenon is still not fully understood, which has limited the development of efficient biomarkers and precision medicine approaches as an alternative that could improve the clinical outcomes of these patients. With the aim of providing an integrative landscape, we review the most recent genomic and epigenomic features attributed to chemoresponse in TGCT patients, highlighting how we can seek to combat cisplatin resistance through the same mechanisms by which TGCTs are particularly hypersensitive to therapy. In this regard, we explore ongoing treatment directions for resistant TGCT and novel targets to guide future clinical trials. Through our exploration of recent findings, we conclude that epidrugs are promising treatments that could help to restore cisplatin sensitivity in resistant tumors, shedding light on potential avenues for better prognosis for the benefit of the patients.

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy.

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.

Inadequate prediction of postoperative complications in breast cancer surgery: An evaluation of the ACS Surgical Risk Calculator.

BACKGROUND: The American College of Surgeon (ACS) Surgical Risk Calculator is an online tool that helps surgeons estimate the risk of postoperative complications for numerous surgical procedures across several surgical specialties. METHODS: We evaluated the predictive performance of the calculator in 385 cancer patients undergoing breast surgery. Calculator-predicted complication rates were compared with observed complication rates; calculator performance was evaluated using calibration and discrimination analyses. RESULTS: The mean calculator-predicted rates for any complication (4.1%) and serious complication (3.2%) were significantly lower than the observed rates (11.2% and 5.2%, respectively). The area under the curve was 0.617 for any complication and 0.682 for serious complications. p Values for the Hosmer-Lemeshow test were significant (<.05) for both outcomes. Brier scores were 0.102 for any complication and 0.048 for serious complication. CONCLUSIONS: The ACS risk calculator is not an ideal tool for predicting individual risk of complications following breast surgery in a Mexican cohort. The most valuable use of the calculator may reside in its role as an aid for patient-led surgery planning. The possibility of introducing breast surgery-specific data could improve the performance of the calculator. Furthermore, a disease-specific calculator could provide more accurate predictions and include complications more frequently found in breast cancer surgery.