“A very interesting information contributed by the National Cancer Institute is that the percentage of active extracts of marine origin is very superior to the terrestrial one», Fernando de la Calle, Chief of the Department of Microbiology in PharmaMar.
The spanish biophama PharmaMar, world leader in marine biotechnology and that has the mayor world´s collection of samples from marine organisms, comprising 200.000 species, currently has three compounds in different stages of clinical development for the treatment of solid and hematological tumors: plitidepsina, PM1183 y PM184.
Do you want to discover the action mechanisms of the pipeline developed by this company? We give you the keys below.
Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. It specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in tumor cell death via apoptosis (programed death). The bind of plitidepsina to eEF1A2 blocks its pro-oncogenic property and avoids the transport of the badly sequenced proteins (which are toxic for the tumor) to the proteasome, preventing by this way their destruction. Also it prevents the activation of the agresome by eEF1A2 and its destruction in the lisosome. This provokes an excess of proteins badly sequenced and the cellular death by apoptosis. Other treatments are complementary to plitidepsina and block the proteasome or the cereblon which identifies the proteins badly sequenced.
Plitidepsin has seen its marketing authorization application accepted by the EMA in Q4 2016 in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma. It is in clinical development for other hematological cancers, including a Phase Ib trial in relapsed or refractory multiple myeloma as a triple combination of plitidepsin, bortezomib and dexamethasone, and a Phase II study in relapsed or refractory angioimmunoblastic T-cell lymphoma.
It has also received orphan drug designation in the European Union and the United States of America.
Trabectedin and Lurbinectedin are two selective inhibitors of trans-activated RNA polymerase II transcription. They selectively block the elongation phase of messenger RNA synthesis performed by RNA polymerase II. They do not inhibit RNA polymerase I or mitochondrial RNA polymerase, nor do they affect basal transcription: their action mechanism very selectively inhibits RNA polymerase II transcription.
This mechanism is reflected in clinical results, since some tumors present transcriptional addiction (e.g. translocation-related sarcomas, small cell lung cancer, and triple negative breast cancer). These are clear examples of tumors that are sensitive to lurbinectidin.
«In such a difficult disease setting with so few therapeutic options, lurbinectedin has shown encouraging data so far in terms of efficacy and tolerability. As the ATLANTIS phase III nears enrollment completion around mid-year, there is growing anticipation to see if the phase III data will offer these patients in this setting the first new therapeutic option since over twenty years ago», Dr Farago said, oncologist form the Massachusetts General Hospital, and the lead investigator of the III phase essay ATLANTIS, for the treatment of small-cell lung cancer with lurbinectedin in combination with doxorubicin.
PM184 is a marine-derive drug found in a sponge called Lithoplocamia lithistoides. This drug candidate is a microtubule inhibitor that targets a protein called tubulin in a novel way. It blocks cancer growth by impairing cell division of tumor cells through the inhibition of a crucial process called mitosis. It is currently being investigated in a Phase II trial for hormone-receptor positive, HER2-negative locally advanced and/or metastatic breast cancer and in studies in various solid tumors and in other Phase II solid tumor trials.
“Undoubtedly, is in the area of cancer where the metabolic marine arsenal plays the most determinant role, but it is not the only one. The survival to big depths carries structures capable of resisting more than hundred atmospheres of pressure preserving their vital capacity, as the case of certain sponges and gorgonias, and we can use these biomaterials in osseous transplants by their exquisite resistance and flexibility. The neurotoxins of dinoflagelates and mollusks play a determinant role as paarlyzer poisons of vertebrates and nowadays already there have been commercialized certain peptides of marine origin for the treatment of the pain. » Fernando de la Calle, Chief of the Department of Microbiology in PharmaMar.
References:
Olmedo-García et al. Activity of lurbinectedin as single agent and in combination in patients with advanced small cell lung cancer (SCLC). Annals of Oncology (2017) 28 (5): 539-542. doi: 10.1093/annonc/mdx386.
Martínez-Díaz et al. PM060184, a new tubulin binding agent with potent antitumor activity including P-glycoprotein over-expressing tumors. Biochem Pharmacol. 2014 Apr 1;88(3):291-302. doi: 10.1016/j.bcp.2014.01.026. Epub 2014 Jan 31.
*You can acces to clinical essays with plitidepsina trough clinicaltrials.gov and clinicaltrialsregister.eu.
*You can acces to clinical essays with PM1183 through clinicaltrials.gov and clinicatrialsregister.eu.
*You can acces to clinical essays with PM184 through clinicaltrials.gov.