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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.
The oxygen effect and therapeutic approaches to tumour hypoxia
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
Michael R. Horsman, J. Martin Brown, Albert J. van der Kogel, Bradly G. Wouters, Jens Overgaard
The inadequate vascular supply to tumours is one of the major factors responsible for the development of hypoxia. The tumour vasculature develops from normal tissue vessels by the process of angiogenesis. This is an essential aspect of tumour growth, but this tumour neo-vasculature is primitive and chaotic in nature and is often unable to meet the oxygen demands of rapidly expanding tumour regions, thus causing hypoxia to develop. The importance of the tumour neo-vasculature in determining growth and the environmental conditions within a tumour therefore makes it an attractive target for therapy (20). The first and most popular is the use of drugs to prevent angiogenesis from occurring (angiogenesis inhibitors [AIs]), while the second involves the use of therapies that can specifically damage an already established vasculature (vascular disrupting agents [VDAs]). Examples of AIs clinically tested include inhibitors of vascular endothelial growth factor such as bevacizumab; tyrosine kinase inhibitors including sorafenib (Bay 43-9006/nexavar), sunitinib (SU11248/sutent), vanatanib (PTK787/ZX 222584) and vandetanib (ZD6474/zactima); and thalidomide and related analogues (lenalidomide, pomalidomide). Clinically relevant VDAs include tubulin binding agents like combretastatin A-1 phosphate, OXi4503, ombrabulin (AVE8062) and plinabulin (NPI-2358); the flavonoid compound vadimezan (ASA404); and chemotherapeutic drugs such as the vinca alkaloids and arsenic trioxides.
Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds
Published in Expert Opinion on Investigational Drugs, 2019
Marco Tagliamento, Carlo Genova, Giovanni Rossi, Simona Coco, Erika Rijavec, Maria Giovanna Dal Bello, Simona Boccardo, Francesco Grossi, Angela Alama
Plinabulin (NPI-2358) is an investigational small molecule drug, categorized as vascular disrupting agent (VDA) for its predominant role in causing tumor vascular collapse, but having also the potential to bind to the colchicine binding-site on tubulin [70]. In a phase I trial, conducted among 8 patients with NSCLC treated with the combination of plinabulin and docetaxel, 2 PR and 4 SD were reported. Fatigue, pain, nausea, diarrhea and vomiting were the most common AEs, with vomiting particularly related to plinabulin [71]. The randomized phase II trial explored whether plinabulin could improve OS over placebo when combined to docetaxel as second-line. The mOS was 8.7 months (95% CI 6.6–12.6) with plinabulin 30 mg/m2 vs. 7.5 months (95% CI 6.3–10.5) with placebo. A greater difference was observed in the subgroup of patients with tumor dimension > 3 cm pretreated with first-line chemotherapy. In addition it is important to point out that the duration of response was largely in favor of the combination regimen: 12.7 vs. 1.5 months (p = 0.049). The most common AEs were nausea, fatigue, diarrhea, constipation, and anorexia [72].
Prophylaxis and treatment strategies for optimizing chemotherapy relative dose intensity
Published in Expert Review of Anticancer Therapy, 2021
Michelle Shayne, R. Donald Harvey, Gary H. Lyman
Plinabulin is a small molecule that binds to β-tubulin and prevents microtubule polymerization. It is being investigated as both an anti-tumor agent and a neutropenia-preventative agent. Plinabulin has demonstrated anti-tumor activity in vitro against several human tumor cell lines through the induction of apoptosis and anti-angiogenic effects [107–110]. Preclinical studies have also revealed that plinabulin prevents the development of CIN in rodents but does not affect the bone marrow or blood G-CSF levels [111]. These findings have been confirmed in clinical studies, with noninferiority observed versus pegfilgrastim in the number of days of severe neutropenia in a phase 2 randomized study of plinabulin versus pegfilgrastim in 55 NSCLC patients treated with docetaxel [112]. Additionally, results of the phase 3 PROTECTIVE-2 study of plinabulin plus pegfilgrastim compared to pegfilgrastim alone demonstrated that the plinabulin combination results in a significant reduction in the incidence of grade 4 neutropenia, febrile neutropenia, and the duration of profound and severe neutropenia in cycle 1 during TAC treatment in 211 randomized breast cancer patients [113]. The combination regimen also increased the percentage of patients achieving RDI >85% [114]. The safety profile of plinabulin appears manageable. In a phase 1 study in 15 NSCLC patients treated with docetaxel plus plinabulin, the most common adverse events were fatigue, pain, nausea, diarrhea, and vomiting [115]. Furthermore, less bone pain and fewer grade 4 adverse events occurred with plinabulin plus pegfilgrastim versus pegfilgrastim alone in the PROTECTIVE-2 study, and less bone pain was also observed with plinabulin versus pegfilgrastim in the phase 2 study highlighted above in NSCLC [112,113].
Grade 4 Neutropenia Frequency as a Binary Risk Predictor for Adverse Clinical Consequences of Chemotherapy‑Induced Neutropenia: A Meta-analysis
Published in Cancer Investigation, 2023
Ramon Mohanlal, Stephan Ogenstad, Gary H. Lyman, Lan Huang, Douglas W. Blayney
These studies had reported data on 4 (∼50%), ≥6 (38.9%), or <4 (1.1%) cycles. Studies were published in the past ∼20 years: 19 between 2011 and 2021, 14 between 2000 and 2010, and 3 prior to 2000. The plinabulin studies were conducted between 2017 and 2020 and had 4 cycles of treatment in each study. For infection assessment, we only included bacterial and fungal infections, as these are ANC-dependent. Supplemental information is provided in Supplementary Appendix A.