MECHANISTIC INSIGHTS INTO BREAST CANCER DRUG RESISTANCE

• Author Information

  Abhishek Jayswal, Atish Waghmare

• Abhishek Jayswal, Atish Waghmare
• MECHANISTIC INSIGHTS INTO BREAST CANCER DRUG RESISTANCE

Abstract

Breast cancer remains one of the most prevalent and life-threatening malignancies worldwide, characterized by remarkable molecular heterogeneity and complex therapeutic challenges. Despite substantial progress in surgery, chemotherapy, radiotherapy, endocrine therapy, and targeted treatments,
the emergence of drug resistance continues to limit therapeutic success and contributes significantly to cancer-associated mortality, recurrence, and metastasis. Drug resistance in breast cancer occurs in two major forms: intrinsic resistance, which exists prior to treatment due to pre-existing genetic and epigenetic alterations, and acquired resistance, which develops progressively after an initial response to therapy. Multiple molecular and cellular mechanisms contribute to resistance, including overexpression of drug efflux transporters, enhanced DNA repair, dysregulation of apoptotic pathways, activation of compensatory signaling cascades such as PI3K/AKT/mTOR, epithelial–mesenchymal transition, cancer stem cell enrichment, and alterations in the tumor microenvironment. Resistance mechanisms vary among hormone receptor-positive, HER2-positive, and triple-negative breast cancer subtypes, further complicating treatment strategies. Additionally, growing evidence suggests that phytochemicals and novel targeted approaches may help overcome therapeutic resistance and improve treatment outcomes. This review comprehensively discusses the major mechanisms underlying breast cancer drug resistance and highlights emerging therapeutic strategies aimed at enhancing clinical efficacy and patient survival.
Keywords: Breast cancer; Drug resistance; Molecular mechanisms; Targeted therapy; Phytochemicals.

Review Article