A phase I and pharmacokinetic study of elisidepsin (PM02734) in patients with advanced solid tumors

Salazar, Ramón; Jones, Robert J.; Oaknin, Ana; Crawford, Donna; Cuadra, C.; Hopkins, C. A.; Gil, Marta; Coronado, C.; Soto-Matos, Arturo; Cullell-Young, Martín; Dios, Jorge Luis Iglesias; Evans, T.R. Jeffry

doi:10.1007/s00280-012-1951-6

Cited by 19 publications

(10 citation statements)

References 24 publications

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“…reported that acquired resistance to elisidepsin in cancer cells is associated with a switch to the epithelial‐mesenchymal transition (EMT) state, which may be seen as a hallmark of cancer progression to the invasive and metastatic disease . This compound displayed in vivo anticancer activity against human melanoma, liver, pancreas, breast, and prostate cancer xenografts …”

Section: Mollusk‐derived Anticancer Agentssupporting

confidence: 63%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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Section: Mollusk‐derived Anticancer Agentssupporting

confidence: 63%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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show abstract

“…It showed promising results for further clinical studies of cancer therapy. Some clinical trials were submitted, including a study of elisidepsin in patients with advanced solid tumors [ 57 ]. The anticancer cyclic depsipeptide plitidepsin was isolated from the Mediterranean tunicate Aplidium albicans [ 58 ].…”

Section: Natural Cyclic Peptides and Analogues In Clinical Trialsmentioning

confidence: 99%

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

2018

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Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein.

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“…These results were promising and gave a rational basis for further investigations such as clinical studies of cancer treatment. A few clinical trials were submitted, they were the study of elisidepsin in patients with advanced solid tumor [ 184 ] and the study of combination therapy with erlotinib in patients with advanced malignant solid tumors. The two studies have been completed and the pharmaceutical company decided to suspend the development of elisidepsin in 2012 in view of commercial unviability of this product.…”

Section: Marine Peptide Products In Market and Clinical Trialsmentioning

confidence: 99%

Marine Peptides: Bioactivities and Applications

2015

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Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.

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A phase I and pharmacokinetic study of elisidepsin (PM02734) in patients with advanced solid tumors

Abstract: Elisidepsin is well tolerated with predictable reversible transaminase increases. Encouraging preliminary evidence of antitumor activity was observed.

Cited by 19 publications

References 24 publications

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

Marine Peptides: Bioactivities and Applications

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