Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy

Abstract

Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherapy, and to prevent formation of drug resistant cancer cells. It is also necessary to prevent the formation of cancer progenitor cells by epigenetic mechanisms, as cancer progenitor cells are insensitive to standard therapies. In this article, we emphasize the role for the rational development of combination therapy, including epigenetic drugs, in achieving these goals.

Transcriptional activation of cyclin D1 via HER2/HER3 contributes to cell survival and EGFR tyrosine kinase inhibitor resistance in non-small cell lung carcinoma

“…These data suggest that EGFR 19del knockout may simulate EGFR-TKI resistance. This is in agreement with the fact that drug resistance leads to tumor hyper-progression 29 . A recent study provided a proof-of-concept of therapeutic benefits of EGFR knockout in EGFRmutant NSCLC 30 .…”

Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study

“…Thus, it may not be surprising that MIR21 was the most responsive methylation locus to chemotherapeutic drugs. In recent years, there is a growing interest in the mechanistic, biomarker, and therapeutic roles of epigenetic pathways in response to chemotherapy [17,21,22]. The convergence of DNA methylation and microRNA as two potential epigenetic mechanisms on the same VMP1/MIR21 region in response to Fig.…”

Gilteritinib induces PUMA‐dependent apoptotic cell death via AKT/GSK‐3β/NF‐κB pathway in colorectal cancer cells

“…Besides, p53-dependent and/or -independent PUMA induction also intercedes apoptotic response to other targets, such as the drug sunitinib, a multi-kinase inhibitor, 46 and 17-AAG, an Hsp90 inhibitor. 48 Assessing the effectiveness of PUMA-mediated apoptosis can be used to unravel potent antitumour agents that surpass chemoresistance. 38 Chemotherapy is majorly limited through drug resistance, especially in the case of targeted therapies.…”

“…38 Chemotherapy is majorly limited through drug resistance, especially in the case of targeted therapies. 48 Assessing the effectiveness of PUMA-mediated apoptosis can be used to unravel potent antitumour agents that surpass chemoresistance. Recent years have seen the development of a number of apoptosis-targeting agents in various clinical trials.…”