Telomerase and drug resistance in cancer

Abstract

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

“…Cisplatin, a traditional chemotherapeutic drug, has been widely applied in treating human solid malignancies, including nasopharyngeal, oesophageal, and lung carcinoma, ovarian cancer, and glioma (Rocha et al 2015;Gong et al 2018;Okamoto et al 2018). Cisplatin can interact with DNA and activate apoptotic signalling transduction, which is also negatively regulated by prosurvival factors, such as Bcl-2 family members, PI3K/Akt, and various drug efflux pumps (e.g., ABCB1, also named P-gp or MDR1) (Wijdeven et al 2016;Lipinska et al 2017). Considering the development of drug resistance, patients have to receive high doses of cisplatin, thereby leading to undesirable side effects (Sprauten et al 2012).…”

RNF138 confers cisplatin resistance in gastric cancer cells via activating Chk1 signaling pathway

“…Cisplatin generates DNA adducts, which results in strand cross-linking, and activates the DNA damage associated response, eventually leading to apoptosis. On the other hand, the DNA repair pathways are also activated in cancer cells exposed to cisplatin, resulting in inhibition of the apoptotic machinery and thereby increased GC cell survival [5][6][7][8][9][10] .…”

An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics

“…Longer telomeres at relapse could be associated with treatment as observed in chronic myeloid leukemia 57 . Therapy targeting telomerase/telomeres should be further explored in MM as lengthened telomeres may provide a mechanism for treatment resistance 58 .…”