Malignant pleural mesothelioma (MPM) is a rare but invasive cancer, which mainly arises from mesothelial tissues of pleura, peritoneum and pericardium (Wadowski et al., 2020). 80% of MPM arises in pleura (Hung and Chirieac, 2020). Annual statistics indicate that around 30,000 new cases are diagnosed and nearly 25,000 MPM patients die globally (Bray et al., 2018, Yap et al., 2017). Despite significant advances in treatments, the prognosis of MPM patients remains poor, and the 5-year survival rate is less than 10% (Viscardi et al., 2020). Epithelioid, sarcomatoid and biphasic are three main histological subtypes of MPM (Saji et al., 2018), and patients with sarcomatoid histology have the worst survival (Viscardi et al., 2020).

Numerous studies have revealed that asbestos exposure is a major risk factor for MPM (Wadowski et al., 2020, Viscardi et al., 2020). It has been reported that asbestos induces the production of reactive oxygen/nitrogen species in mesothelial cells and macrophages leading to DNA damage (Okazaki, 2022, Dostert et al., 2008, Carbone et al., 2019). Besides, the accumulation of asbestos fibers triggers chronic inflammation to release pro-inflammatory molecules, which results in the MPM (Vogl et al., 2021). Unfortunately, it is estimated that 125 million people are exposed to asbestos due to work in the world (Remon et al., 2015). However, to make matters, the incubation period of MPM is around 40 years after asbestos exposure (Cinausero et al., 2019). Moreover, the use of asbestos is increasing in developing countries despite its use has been prohibited in 55 countries (Remon et al., 2015, Cakiroglu and Senturk, 2020). Therefore, the incidence rate of the global MPM is still elevating every year.

For patients with resectable MPM, surgery including macroscopic complete resection (MCR) is one of options in treatment combined with neoadjuvant chemotherapy or postoperative radiation (Viscardi et al., 2020). However, surgical treatment is not a suitable choice for unresectable MPM. Therefore, front-line polychemotherapy is a standard therapy for patients with unresectable MPM (Viscardi et al., 2020). To date, the combination of cisplatin and pemetrexed is the first-line polychemotherapy for MPM (Vogelzang et al., 2003). Besides, gemcitabine and carboplatin are other options for first-line treatment (Viscardi et al., 2020). Unfortunately, there is no standard second-line chemotherapy for nearly all MPM patients (Viscardi et al., 2020). Moreover, radiotherapy is useful for all MPM patients to prevent postoperative recurrence (de Perrot et al., 2017). In addition, immunotherapy including immune checkpoint inhibitors (ICIs) is considered as a promising modality for the treatment of MPM (Liao et al., 2021). Despite significant advances in therapies for MPM, the effective therapies for MPM are still limited due to the resistance to existing therapies. Therefore, it is urgent to explore novel therapeutic targets for the treatment of MPM.

Growing evidence has indicated that non-coding RNAs (ncRNAs) are emerging as critical players in cancer progress (Anastasiadou et al., 2018, Li et al., 2020). Of these, long non-coding RNAs (lncRNAs) potentially could be promising therapeutic targets for numerous cancers (Liu et al., 2021a, Bhan et al., 2017). In this regard, lncRNAs might also potentially therapeutic targets for MPM. Thus, this review provides a comprehensive overview of roles of lncRNAs in MPM to implement them as promising therapeutic targets for MPM.

A total of 152 guidance and published studies between 2003 and 2022 searched in PubMed using “malignant pleural mesothelioma” and “long non-coding RNA” as keywords were read. The search strategies met the following criteria: (1) the guidance and articles were published in English; (2) both text words and references were clearly included; (3) data in published articles were believable.