Breast Cancer CDK4/6 Inhibitor Resistance and Immunotherapy Strategies

Abstract

Breast cancer remains the most common cancer among women worldwide. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as key targeted therapies. They primarily prevent tumor growth in hormone receptor-positive breast cancer by blocking the cell cycle. These drugs not only directly slow down cell growth but also significantly alter the tumor immune microenvironment in important ways. They enhance antigen presentation, facilitate T-cell infiltration into tumors, and reduce the activity of regulatory T cells that suppress immune responses. In clinical practice, drug resistance remains a major issue. This resistance may be present from the outset or develop over time, greatly limiting the long-term efficacy of these drugs. This article reviews the two main ways in which CDK4/6 inhibitors exert their effects. One is to directly block the cell cycle, and the other is to reshape the immune microenvironment. The article also discusses various reasons for drug resistance and explores solutions to this problem. Combination therapy is one option. Its purpose is to provide theoretical support for improving this targeted treatment approach. However, there is still a major issue. The existing CDK4/6 inhibitors are not effective for all subtypes. They have poor efficacy in triple-negative breast cancer. This subtype has the highest mortality rate, grows rapidly, and lacks targeted treatment options. Research is needed to expand the use of these drugs. The research should focus on the forms of resistance and also on under-served subtypes such as triple-negative breast cancer. This work is urgent and will help improve the treatment outcomes for all breast cancer patients.