CDK6

This study investigated additional genetic alterations in MET-amplified gastric cancers (GCs), which are associated with poor prognosis and limited response to targeted therapies. Researchers found that MET amplification is frequently accompanied by co-amplifications of other oncogenes located on chromosome 7, such as BRAF, CDK6, and EGFR, in 54% of cases. These co-amplifications exhibit significant intra- and intertumoral heterogeneity. This complex heterogeneity may explain the diagnostic and therapeutic challenges, subclonal evolution, and the failure of targeted therapies in MET-amplified GCs.

Improved survival rates for reproductive-age breast cancer patients highlight significant oncofertility challenges. Fertility preservation, gonadotoxicity, and pregnancy safety are key concerns requiring early and integrated management within the therapeutic plan. Prompt referral for fertility preservation is crucial, ensuring it does not compromise oncologic outcomes. Modern therapies such as PARP inhibitors, CDK4/6 inhibitors, HER2-monoclonal antibodies, and endocrine treatments raise specific questions due to a lack of prospective human fertility data. A precautionary approach is recommended, including effective contraception and adherence to washout periods.

The treatment paradigm for hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) has significantly evolved from sequential therapies to more personalized strategies. CDK4/6 inhibitors combined with endocrine therapy remain the first-line standard of care, consistently improving progression-free survival and, for some agents, overall survival. The emergence of antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan, sacituzumab govitecan, and datopotamab deruxtecan is reshaping the therapeutic landscape, including for HER2-low and HER2-ultralow disease. Metastasis-directed therapy is also considered for oligometastatic or oligoprogressive disease, requiring nuanced decision-making. Overall management now integrates tumor biology, therapeutic advances, and patient-defined goals of care.