The molecular mechanisms of chemoresistance in cancers

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Chemoresistance is a significant obstacle in cancer treatment, leading to disease recurrence, metastasis, and mortality.
• Understanding the molecular underpinnings of multi-drug resistance is critical for improving patient outcomes.

Purpose of the Study:

• To review the diverse molecular mechanisms contributing to intrinsic and acquired chemoresistance in cancer.
• To highlight the roles of specific molecular players including transporter pumps, oncogenes, tumor suppressor genes, and cellular processes like autophagy and EMT.

Main Methods:

• This review synthesizes information from existing literature on chemoresistance.
• It discusses molecular aspects identified through various experimental models, including cell culture and orthotopic models.

Main Results:

• Chemoresistance involves multiple molecular facets: transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk, NF-κB), p53 tumor suppressor gene, mitochondrial alterations, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosomes.
• Chemoresistance-related proteins function at various cellular locations (extracellular, membrane, cytosolic, nuclear) influencing proliferation, apoptosis, EMT, autophagy, and exosome release.
• Complex cross-talk exists between pathways, such as EGFR-Akt-NF-κB signaling affecting apoptosis-related genes (Bcl-2, Bcl-xL, survivin) and EMT-stemness.

Conclusions:

• Clarifying these molecular mechanisms is essential for developing targeted, individualized, and combination therapies.
• Identifying therapeutic targets, screening chemosensitive populations, and evaluating therapeutic efficacy are key steps for overcoming chemoresistance.