Cancer Cells Acquire Resistance to Anticancer Drugs: An Update

Abstract

The efficacy of cancer chemotherapy is often affected by the emergence of resistant can-cer cells. While biochemical and pharmaco-logical mechanisms have been proposed to ex-plain chemo-resistance, the genes involved in this process have not been fully identified. We previously used genomic DNA microarrays and quantitative RT-PCR to identify the genes associated with resistance to chemotherapeutic drugs, particularly to the genotoxic agent cisplatin. Notably, knockdown of the cisplatin resistance (CPR) genes that we identified was shown to reduce chemoresistance and to suppress the growth of tumor xenographs in cisplatin-treated mice, indicating that the newly identified CPR genes may represent potential therapy candidates to limit chemo-resistance and to improve the efficacy of anticancer drugs. In addition to genetic mutations, re-searchers have found that epigenetic changes and alternative splicing of specific genes may also allow cancer cells to become resistant to chemotherapeutic drugs. In this article, the authors present an overview of the latest findings in this field, including genetic changes, epigenetic changes and alternative splicing.

Cytotoxic activity of ten algae from the Persian Gulf and Oman Sea on human breast cancer cell lines; MDA-MB-231, MCF-7, and T-47D

“…There are many chemotherapeutic agents used in the treatment of breast cancer. Nevertheless, due to the high side effects and resistance of cancer cells to these drugs,[ 3 4 5 ] there is still urgent need to develop new and more efficient therapeutic agents to battle the disease.…”

RAC1b Overexpression Confers Resistance to Chemotherapy Treatment in Colorectal Cancer

“…However, approximately 40% of colorectal cancer become refractory to FOLFOX. The development of resistance occurs by several processes, like enhanced DNA damage repair, altered expression of oncogenes, reduced apoptosis, decreased drug import, and enhanced tolerance to platinum adduct accumulation (3,45). One of the major clinical challenges in treating colorectal cancer is identifying the subset of patients who will respond to chemotherapy or alternatively, identifying patients that will be resistant to chemotherapy.…”

Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells

“…However, this view has been challenged by numerous recent studies demonstrating that in several metastatic cancers, OxPhos is the predominant ATP cellular supplier in strong preference over glycolysis (Moreno-Sánchez et al, 2007;Ralph et al, 2010;Zu and Guppy, 2004). Thus, active OxPhos and mitochondrial remodeling and ROS production have been associated with invasiveness onset (Zhao et al, 2013), metastatic and malignant phenotype acquisition Ralph et al, 2015), cellular cycle activation and autophagy resistance (Salem et al, 2012), and other mechanisms implicated in drug resistance (Indran et al, 2011;Lu and Chao, 2012).…”