Emerging role of non-coding RNAs in resistance to platinum-based anti-cancer agents in lung cancer

Abstract

Platinum-based drugs are the first line of therapeutics against many cancers, including lung cancer. Lung cancer is one of the leading causes of cancer-related death worldwide. Platinum-based agents target DNA and prevent replication, and transcription, leading to the inhibition of cell proliferation followed by cellular apoptosis. About twenty-three platinum-based drugs are under different stages of clinical trials, among cisplatin, carboplatin, and oxaliplatin are widely used for the treatment of various cancers. Among them, cisplatin is the most commonly used drug for cancer therapy, which binds with RNA, and hinders the cellular RNA process. However, long-term use of platinum-based drugs can cause different side effects and has been shown to develop chemoresistance, leading to poor clinical outcomes. Chemoresistance became an important challenge for cancer treatment. Platinum-based chemoresistance occurs due to the influence of intrinsic factors such as overexpression of multidrug resistance proteins, advancement of DNA repair mechanism, degradation, and deactivation of intracellular thiols. Recently, epigenetic modifications, especially non-coding RNAs (ncRNAs) mediated gene regulation, grasp the attention for reversing the sensitivity of platinum-based drugs due to their reversible nature without altering genome sequence. ncRNAs can also modulate the intrinsic and non-intrinsic mechanisms of resistance in lung cancer cells. Therefore, targeting ncRNAs could be an effective approach for developing novel therapeutics to overcome lung cancer chemoresistance. The current review article has discussed the role of ncRNA in chemoresistance and its underlying molecular mechanisms in human lung cancer.

Transcriptomic Analysis Reveals Early Alterations Associated with Intrinsic Resistance to Target Therapy in Lung Adenocarcinoma Cell Lines

“…Numerous studies have explored the mecha-nisms of acquired resistance, usually analyzing this phenomenon after multiple rounds of exposure to therapeutic drugs [35][36][37]. Intrinsic resistance, denoting the inherent or natural resistance of cancer cells to specific treatments or drugs, has recently become a subject of exploration [38]. Initial investigations into this drug resistance mechanism have been conducted in diverse lung cancer cell lines, with additional insights gleaned from information available in public databases [39].…”

Role of long non-coding RNA in chemoradiotherapy resistance of nasopharyngeal carcinoma

“…Platinum drugs are cytotoxic drugs used as first-line chemotherapeutic agents for many cancers. Their mode of action involves binding to DNA after hydrolyzing one or two chloride ions in the body, thereby impeding replication and transcription and, consequently, the proliferation of cancer cells ( 35 , 36 ). However, prolonged usage of platinum-based drugs may lead to the development of resistance, which can compromise treatment efficacy.…”

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

“…84 A variety of reasons contribute to treatment resistance, including multi-drug resistance, apoptosis suppression, specific genetic or epigenetic alterations, enhancing DNA repair in cancer cells, and so on. [85][86][87] Therefore, exploiting the RNA-cleaving DNAzymes to target the treatment resistance-related genes may be a promising therapeutic strategy to enhance the efficacy of cancer therapy. As a kind of innate or acquired resistance, chemoresistance is the main cause of the clinical failure of chemotherapy.…”