Using bioinformatics and artificial intelligence to map the cyclin-dependent kinase 4/6 inhibitor biomarker landscape in breast cancer.

Abstract

A cyclin-dependent kinase 4/6 (CDK4/6) inhibitor combined with endocrine therapy is the standard-of-care for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. However, not all patients respond to the treatment, resistance often occurs and efficacy outcomes from early breast cancer trials have been mixed. To identify biomarkers associated with CDK4/6 inhibitor response or resistance, we combined bioinformatic-database analyses, artificial intelligence-assisted literature review, and manual literature review (Embase and OVID Medline; search window: January 2012-October 2022) to compile data to comprehensively describe the CDK4/6 inhibitor biomarker landscape. Based on these results, and validation by external experts, we identified 15 biomarkers of clinical importance (AR , AURKA, ERBB2, ESR1, CCNE1, CDKN1A/B, CDK2, CDK6, CDK7, CDK9, FGFR1/2, MYC, PIK3CA/AKT, RB1 and STAT3) that could guide future breast cancer research.