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Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35005994/
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently established as standard therapies in combination with endocrine therapy as first- and second-line systemic treatment options for both endocri ...
Relevance: The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. Individual molecular candidates with robust and reliable evidence are discussed in more depth.
• Source: JCO Precision Oncology
• Relevance: “We can now identify patient populations that will respond poorly to CDK4/6 inhibition through tumor profiling and next-generation sequencing of liquid biopsies before starting treatment and have the opportunity to consider switching to alternative treatment strategies.”
• In this systematic review, the authors identified resistance biomarkers for cyclin-dependent kinase 4/6 inhibition in metastatic breast cancer by mining recent molecular data. Multiple mechanisms were identified including the loss of retinoblastoma-1 function, aberrant cyclin-E signaling, and CDK6 activity in some patients. These resistance mechanisms were identified using circulating tumor DNA and tumor biopsies. There are, however, many molecular resistance mechanisms that need to be elucidated.
• The clinical relevance of these findings is that researchers can now identify poorly responding patient populations to CD4/6 inhibitors before initiating treatment. These populations can be identified via tumor profiling and NGS of liquid biopsies. These screening modalities will allow switching treatments or finding alternatives.