Tumor-promoting aftermath post-chemotherapy: A focus on breast cancer

Abstract

Chemotherapy is an important tool for the management of solid tumors including breast cancers (BC). Its neo-adjuvant and adjuvant use is important for shrinking tumor size and neutralizing the disseminated cancer cells. Initial chemotherapy administration often leads to a reduction in tumor size and pathological complete response. However, chemotherapy-induced tumor-free survival is not durable in BC patients. Chemotherapy is the prominent treatment for the management of triple-negative BC (TNBC), the most aggressive subtype of the BC. Various factors such as the emergence of multidrug resistance (MDR), the appearance of dormant and tolerant clones, and remodeling of the tumor microenvironment (TME) in response to chemotherapy-induced stress are responsible for tumor relapse. In current review, the authors have highlighted various cytokines and growth factors, and underlying signaling pathways such as NF-κB and PI3k/AkT, responsible for the emergence of chemo-resistance and metastasis in the TME. The present review potentially explores the role of epithelial-mesenchymal transition (EMT) in eliciting metastasis and providing stem-like phenotypes to the BC cells. The appearance of drug-tolerant sub-populations such as persister cells and BC stem cells has been discussed with mechanistic pathways. Through the current review, authors have significantly explained the mechanistic pathways of the chemotherapy-induced transformation of the tumor microenvironment (TME) constituents responsible for tumor progression. Potential therapeutic targets have been highlighted.

Keywords: Cancer stem cells; Metastasis; Multidrug resistance; Persister cells; TMEM.