The Role of N⁶-Methyladenosine RNA Modification in Platinum Resistance

Abstract

N⁶-methyladenosine (m6A) RNA methylation, a dynamic regulator of transcript expression, plays a pivotal role in cancer by influencing diverse mRNA processes, including nuclear export, splicing, translation and decay. It intersects with cancer biology, impacting progression, treatment sensitivity and prognosis. Platinum-based compounds are essential in cancer treatment, while intrinsic or acquired resistance poses a formidable challenge, limiting therapeutic efficacy. Recent breakthroughs have established a direct association between m6A RNA methylation and platinum resistance in various cancer types. This review summarized related studies, aiming to provide profound insights into the interplay between m6A-associated regulation and platinum-resistance mechanisms in cancer. It explores therapeutic approaches, including personalized treatments based on m6A profiles, guiding future research to enhance clinical strategies for oncological prognostic outcomes.

Plain language summary

Cancer poses a global health challenge, with platinum-based drugs as a cornerstone of treatment. Regrettably, cancer cells can develop resistance to these drugs, diminishing their effectiveness. Recent research suggests that a subtle modification known as N⁶-methyladenosine (m6A) on RNA molecules may contribute to this resistance. m6A acts as a minuscule tag on RNA molecules within the cells, akin to a genetic switch. When altered, it can render cancer cells less responsive to platinum-based drugs. Scientists have found that m6A changes in various cancer types can bolster resistance to platinum-based drugs. This reduced drug efficacy presents a significant concern, as platinum-based drugs are vital in treating diverse cancer types, including ovarian, lung and colorectal cancer. Understanding the impact of m6A on platinum resistance is pivotal. It may enable doctors to identify patients less likely to respond to treatment. Researchers are also investigating methods to target m6A alterations in cancer cells, potentially rendering them more receptive to platinum-based drugs. Ongoing research into m6A and its role in platinum resistance holds promise for enhancing cancer treatments, ultimately increasing the chances of success for patients requiring platinum-based drugs.

Tweetable abstract

Unlocking cancer’s resistance to platinum drugs: #m6A RNA changes hold the key; Personalized treatment approaches on the horizon; #CancerResearch; #PrecisionMedicine.

Keywords::

• cancer
• m6A RNA modification
• platinum resistance
• prognostic outcomes

Author contributions

X Chen, K Wang and L Wang designed the study and participated in writing the original draft. X Chen and L Wang carried out supervision; J Gu was responsible for funding acquisition; X Chen conducted validation of the results. All the authors have read and approved the final manuscript.

Acknowledgments

The authors appreciate the researchers whose data were used in the study and analysis.

Financial disclosure

This study was financially supported by the National Natural Science Foundation of China (grant no. 382273348), the National Key R&D Program of China (grant nos. 2022YFC2704200 and 2022YFC2704203) and the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (grant no. 2022–175). None of the funding agencies had a role in the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Institutional Review Board of the Taizhou Hospital of Zhejiang Province.

Additional information

Funding

This study was financially supported by the National Natural Science Foundation of China (grant no. 382273348), the National Key R&D Program of China (grant nos. 2022YFC2704200 and 2022YFC2704203) and the Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (grant no. 2022–175). None of the funding agencies had a role in the study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.