Emerging targets in cancer drug resistance

Abstract

Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer treatment. Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct mechanisms and pathways. Understanding the molecular mechanisms involved in drug resistance remains an important area of research for identification of precise targets and drug discovery to improve therapeutic outcomes. This review highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.

Overcoming P-Glycoprotein-Mediated Doxorubicin Resistance

“…This molecular structure accommodates its interaction with major MDR efflux transporters in the ABC superfamily proteins. It has been well established that doxorubicin and other anthracycline derivatives are P-gp substrates with ability to up-regulate P-gp/MDR1 expression after repeated exposure in various cancer cells such as breast and lung cancers as well as in vivo and in clinical settings [66,107,108]. For instance, lung perfusion with doxorubicin resulted in an increase of MDR1 RNA in patients with sarcoma pulmonary metastases [18].…”

Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy

“…Thus, the relationship between genetic disruptions and epigenetic abnormalities are mutually beneficial in order to drive cancer development and could be playing a key role in individual differences displayed by patients in the way they respond to therapies in both toxicity or treatment efficacy (15,46,47). Multiple studies demonstrate that reversing epigenetic patterns through de novo epidrugs and epidrug repurposing can resensitize cancer cells to chemotherapy (48)(49)(50).…”

“…Lately, epigenetic therapy has taken relevance in the field of oncology, where epidrugs have been successfully used in treatment, mostly in combination with standard chemotherapy (52). Epidrugs (with one-target, as well as repurposed epidrugs; see below) that are designed based on these principles can exert direct cytotoxic effects over malignant cells (14,46), function as sensitizers in complementary therapies (53,54), or can be used to overcome epigenetically-acquired drug resistance against the limits of chemotherapy efficacy, as there are the dynamic associations between epigenetic pattern changes and resistance to therapeutic regimes for cancer (50,52,55). New epidrugs compounds are continually being tested for cytotoxicity, pharmacological parameters, and a better understanding of their mode of action; in both preclinical research (in vitro and in vivo) as well as in clinical trials.…”

Curcumin effect on cancer cells' multidrug resistance: An update

“…Therefore, they epigenetically control the expression of genes such as tumor suppressors genes or oncogenes (Jalkanen, Coleman, & Wilusz, 2014). Recent studies have proven that miRNA dysregulation promotes the drug resistance in various cancers (Kumar, Kushwaha, & Gupta, 2019). For example, downregulation of miR-127 and miR-34a reduced apoptosis in the MFC-7 cells treated with doxorubicin by decreasing p53 signaling pathway.…”