Abstract
Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC.
Highlights
Lung cancer is the cancer with the highest mortality accounting for 28% of all cancer deaths, estimated at 1.3 million deaths worldwide every year [1]
As overexpression of EZH2 has been shown to contribute to the development of acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo [156], potentially non-small-cell lung cancer (NSCLC) patients with either high Breast Cancer 1 Gene (BRCA1) or EZH2 levels might potentially benefit from treatments with poly(ADP-ribose) polymerase (PARP) inhibitors such as (DZNep), or could potentially be targeted to induce mIR-101
It is interesting to note that mIR-200 has been shown to target ZEB1 (Table 1) [45,167,168], and as levels of mIR-200c are known to be decreased in NSCLC [46], it may be important to determine the BRCA1 status of these tumors
Summary
Lung cancer is the cancer with the highest mortality accounting for 28% of all cancer deaths, estimated at 1.3 million deaths worldwide every year [1]. Mortality in lung cancer is high due in part to (a) difficulties in detecting it at an early stage and (b) associated resistance to currently available chemotherapy and radiotherapy regimes [3]. If considered as a separate entity, lung cancer in never smokers would still rank as the seventh most common cause of cancer death worldwide [3]. The standard of care for NSCLC includes treatment with a platinum-based chemotherapy regimen [4]. Many patients do not benefit from this treatment and tumors often develop resistance to platinum based therapy. In the following review we shall discuss how epigenetics, a specialized form of gene regulation, and the cellular machinery involved with this regulation may be of critical importance in the development of resistance to cisplatin in NSCLC (Figure 1)
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