A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach

Abstract

The acquisition of resistance to traditional chemotherapy and the chemoresistant metastatic relapse of minimal residual disease both play a key role in the treatment failure and poor prognosis of cancer. Understanding how cancer cells overcome chemotherapy-induced cell death is critical to improve patient survival rate. Here, we briefly describe the technical approach directed at obtaining chemoresistant cell lines and we will focus on the main defense mechanisms against common chemotherapy triggers by tumor cells. Such as, the alteration of drug influx/efflux, the enhancement of drug metabolic neutralization, the improvement of DNA-repair mechanisms, the inhibition of apoptosis-related cell death, and the role of p53 and reactive oxygen species (ROS) levels in chemoresistance. Furthermore, we will focus on cancer stem cells (CSCs), the cell population that subsists after chemotherapy, increasing drug resistance by different processes such as epithelial-mesenchymal transition (EMT), an enhanced DNA repair machinery, and the capacity to avoid apoptosis mediated by BCL2 family proteins, such as BCL-XL, and the flexibility of their metabolism. Finally, we will review the latest approaches aimed at decreasing CSCs. Nevertheless, the development of long-term therapies to manage and control CSCs populations within the tumors is still necessary.

Antibody–drug conjugates in cancer therapy: mechanisms and clinical studies

“…Chemoresistance in cancer cells often occurs when drugs are removed from the cytoplasm through ATP‐binding (ABC) transporters, also known as drug efflux pumps. 411 , 412 , 413 These transporters can also contribute to drug resistance in ADCs because many cytotoxic drugs are substrates of these transporters. P glycoprotein (P‐gp) is identified as the primary factor contributing to resistance against vc‐MMAE‐based conjugates, irrespective of P‐gp expression levels.…”

Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor

“…Similar to normal tissue stem cells, CSCs exhibit significant phenotypic and functional heterogeneity. While CSCs have been reported in a wide spectrum of human tumors, the biology of CSCs in NSCLC remains elusive [ 6 ]. Current anti-cancer therapies fail to eradicate CSC clones and instead favor the expansion of the CSC pool and select for resistant CSC clones, thereby resulting in treatment resistance and subsequent relapse in these patients.…”

Editorial for the Special Issue “Advances in the Development of Anticancer Drugs”

“…In order to address the pivotal issues of resistance to traditional chemotherapy and the chemoresistant metastatic relapse’s contribution to treatment failure and poor cancer prognosis, understanding the mechanisms by which cancer cells navigate chemotherapy-induced cell death and develop resistance is not only critical for enhancing patient survival rates but also imperative for advancing more effective therapies. In their concise review, Perán and colleagues [ 12 ] delineate the methodology and protocol employed to induce drug chemoresistance in cancer cell lines. They subsequently delve into the exploration of the defense mechanisms activated by tumor cells to elude common chemotherapy agents.…”

“…The authors highlight that cancer cell lines employ various strategies, including the alteration of drug influx/efflux, enhanced drug metabolic neutralization, improved DNA repair mechanisms, and the inhibition of apoptosis-related cell death, in the development of chemoresistance. Throughout the discussion, Toledo et al [ 12 ]. examine the roles of p53 and reactive oxygen species levels, with a specific focus on cancer stem cells and the residual cell population post-chemotherapy.…”