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Current and Future Perspectives of Marine Drugs for Cancer Disorders: A Critical Review
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Bhaskaran Mahendran, Thirumalaraju Vaishnavi, Vishakante Gowda, Johurul Islam, Narahari Rishitha, Arunachalam Muthuraman, Rajavel Varatharajan
Various marine-derived products are identified as potential therapeutic efficacy in vitro and in vivo. Some of the marine-derived products are under clinical trials use to treat cancer disorders. The ongoing marine drugs in clinical trials are plinabulin, plitidepsin, glembatumumabvedotin, and lurbinectedin at phase III levels; mafodotin, depatuxizumab, polatuzumab vedotin, tisotumab AGS-16C3F, PM184, vedotin, enfortumabvedotin, and monomethyl auristatin F at phase II levels; GSK2857916, ABBV-085, ABBV-399, ABBV-221, ASG-67E, ASG-15ME, bryostatin, marizomib, and SGN-LIV1A at phase I levels (Dyshlovoy and Honecker, 2018; Mayer, 2017; Doronina et al., 2018). Furthermore, the additional marine-derived products are pipelines for the clinical trials. Some of newer molecules are identified in different marine sources. These molecules proved their potency and efficacy in various ailments in laboratory animals. Therefore, marine-derived natural molecules are expected to manage multiple cancer disorders.
Emerging drugs for small cell lung cancer: a focused review on immune checkpoint inhibitors
Published in Expert Opinion on Emerging Drugs, 2020
Haritha G. Reddy, Angel Qin, Gregory P. Kalemkerian
Lurbinectedin recently received accelerated approval from the FDA based on a single-arm phase II trial that enrolled 105 patients with progression of disease after receiving one prior treatment regimen [26]. Response rate was 35% in all patients, 22% in patients with resistant disease and 45% in those with sensitive disease. In all patients, median PFS and OS were 3.5 months and 9.3 months, respectively, and both survival endpoints were substantially better in patients with sensitive disease. Phase III trials comparing lurbinectedin to standard therapy are on-going. In Japan, amrubicin is available as second-line treatment for SCLC. However, a phase III trial comparing amrubicin vs. topotecan did not demonstrate a survival benefit [27]. In the U.S., two PD-1-targeted ICIs, nivolumab and pembrolizumab, have been FDA-approved for third-line therapy in SCLC based on phase Ib/II clinical trials [28,29].
Lurbinectedin: an FDA-approved inducer of immunogenic cell death for the treatment of small-cell lung cancer
Published in OncoImmunology, 2020
Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Small-cell lung cancer is a disease with a notoriously bad prognosis. The initial treatment is usually a combination of platinum compounds (cisplatin or carboplatin) with etoposide that often leads to a partial or even apparently complete response, yet is invariably followed by a relapse of the disease that then manifests in a chemotherapy-resistant form.12 It should be noted that cisplatin and etoposide are rather poor ICD inducers, providing an explanation for this observation.6,9 Although both drugs kill a substantial portion of tumor cells, they are unable to induce an immune response that would provide long-term effects to the patients. From this perspective, the introduction of a potent ICD inducer like lurbinectedin into the clinics (Figure 1a), initially as a second-line treatment appears a logical development.13 Although the formal proof for this conjecture is still elusive, two interesting future developments await urgent exploration. First, it will be interesting to know whether lurbinectedin might be useful as a first-line treatment, thus avoiding the patient with small-cell lung cancer to endure a debilitating (and perhaps even immunosuppressive) platinum-based chemotherapy (Figure 1b). Second, it will be important to clarify whether lurbinectedin might be advantageously combined with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 interaction (Figure 1c). Indeed, for other cancers, there are multiple examples in which ICD inducers have been successfully combined with ICIs, both preclinically and clinically,9 strongly suggesting that this might be an adequate strategy for the clinical management of small-cell lung cancer.
Lurbinectedin synergizes with immune checkpoint blockade to generate anticancer immunity
Published in OncoImmunology, 2019
Wei Xie, Sabrina Forveille, Kristina Iribarren, Allan Sauvat, Laura Senovilla, Yan Wang, Juliette Humeau, Maria Perez-Lanzon, Heng Zhou, Juan F. Martínez-Leal, Guido Kroemer, Oliver Kepp
Lurbinectedin is a selective inhibitor of active transcription of protein-coding genes20 that is currently undergoing clinical investigation and has recently gained orphan drug approval for the treatment of small cell lung cancer (SCLC). Here, we investigated the capacity of lurbinectedin to stimulate the emission of immunogenic DAMPs and tested anticancer immune responses in three experimental in vivo models. Our results support the contention that lurbinectedin causes immunogenic cell death in tumors and creates anticancer immunity.