Combating chemoresistance in breast cancer: exploring tumour microenvironment, combination therapies and drug repurposing strategies

Chemoresistance in breast cancer (BC) is a challenge that remains paramount in its treatment. Since the current therapies are insufficient to address chemoresistance, more potent strategies are urgently required to enhance current treatment plans. Chemoresistance in cancer can arise from a variety of molecular mechanisms, like drug efflux, decreased drug uptake, enhanced DNA repair mechanisms, the ability of cancer cells to avoid apoptosis, tumour heterogeneity and significant alterations in the tumour microenvironment, where interactions between cancer cells, cancer-associated fibroblasts, immune cells and the extracellular matrix contribute to a supportive environment that allows tumours to survive treatment and escape therapy. The available therapeutic strategies include combination therapies, immunotherapies, epigenetic modulators and drug delivery systems based on nanoparticles are a few promising strategies towards overcoming chemoresistance. Drug repurposing provides a practical and economical means to combat resistance through FDA-approved anticancer agents. Second, the incorporation of immune checkpoint inhibitors (ICIs), PARP inhibitors and metabolic modulators enhances the efficacy of treatments even further. Here in this article, we have reviewed the latest developments in the management of chemoresistance with a focus on innovative therapeutic approaches, innovative therapies targeting the tumour microenvironment, strategic drug repurposing and meticulously designed clinical trials in the treatment of BC.