Journal
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
Volume 15, Issue 3, Pages 305-322Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17512433.2022.2074835
Keywords
Chemoresistance; malignant mesothelioma; microRNA; splicing deregulation; notch; cancer stem cells; targeted therapy
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Funding
- Cancer Center Amsterdam (CCA) Foundation grant 2015
- Italian Association for Cancer Research (AIRC) IG grant [2020-24444]
- Italian Ministry of Education, University and Research
- 'the Law Offices of Peter G. Angelos Grant' from the Mesothelioma Applied Research Foundation (MARF)
- National Science Centre of Poland [2018/31/B/NZ7/02909]
- IDUB [664/256/62-0212]
- European Cooperation in Science and Technology (COST) Action [17104 STRATAGEM]
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Malignant mesothelioma is an aggressive rare cancer associated with asbestos exposure and currently incurable due to drug resistance. The alterations in miRNA and splicing machinery may contribute to chemoresistance. The Notch signaling pathway, frequently deregulated in MMe, is involved in cancer stem cell formation and self-renewal, leading to drug resistance and relapses.
Introduction Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeutic targets. Areas covered Chemoresistance is frequently elicited by microRNA (miRNA) alterations and splicing deregulations. Indeed, several miRNAs, such as miR-29c, have been shown to exert oncogenic or oncosuppressive activity. Alterations in the splicing machinery might also be involved in chemoresistance. Moreover, the Notch signaling pathway, often deregulated in MMe, plays a key role in cancer stem cells formation and self-renewal, leading to drug resistance and relapses. Expert opinion The prognosis of MMe in patients varies among different tumors and patient characteristics, and novel biomarkers and therapies are warranted. This work aims at giving an overview of MMe, with a special focus on state-of-the-art treatments and new therapeutic strategies against vulnerabilities emerging from studies on epigenetics factors. Besides, this review is also the first to discuss the interplay between miRNAs and alternative splicing as well as the role of Notch as new promising frontiers to overcome drug resistance in MMe.
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