Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

Abstract

New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients’ response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors.

Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities

“…Cyclins D and E have been reported to be up-regulated, whereas PTPA has been reported to be down-regulated in cancer and neurodegenerative disease [reviewed in ( Seo and Park, 2020 )]. Cyclins control the cell cycle by modulating Cyclin-dependent kinases (CDKs), and their dysregulation underlies several human cancers ( Krasniqi et al, 2022 ; Wu et al, 2022 ; Sher et al, 2023 ). In addition to cell cycle regulation, Cyclins participate in cellular processes specific to terminally differentiated neurons ( Zhou and Ekström, 2022 ).…”