Drug offers 'breakthrough' in treatment of asbestos-linked cancer(theguardian.com)
theguardian.com
Drug offers 'breakthrough' in treatment of asbestos-linked cancer
https://www.theguardian.com/science/2024/feb/15/drug-offers-wonderful-breakthrough-in-treatment-of-asbestos-linked-cancer
18 comments
It's interesting how this drug works: by depleting arginine. Apparently mesothelioma cells lose the ability to make arginine. I wonder if a low-arginine diet would enhance the effect.
ultimately whether it works or not is up to a pretty complex network of kinetics, but low-arginine diet doesn't seem too plausible because it can be shuttled around between cells to some degree via plasma membrane transporters, produced to some degree from proteolysis etc. (https://www.sciencedirect.com/science/article/pii/S002231662... etc)
the approach, which is actually kind of nuts, supports this assumption: pegargiminase depletes by destroying arginine directly; it is fundamentally a super efficient arginine oxidizer coated in lube, more or less
so it's like in principle most of your cells are making arginine and to some degree puking it out, this drug is chewing up all the free arginine floating around, the cells that can synthesize it are cool but the cells that can't synthesize it starve
the approach, which is actually kind of nuts, supports this assumption: pegargiminase depletes by destroying arginine directly; it is fundamentally a super efficient arginine oxidizer coated in lube, more or less
so it's like in principle most of your cells are making arginine and to some degree puking it out, this drug is chewing up all the free arginine floating around, the cells that can synthesize it are cool but the cells that can't synthesize it starve
Your body usually synthesizes all the arginine it needs, independent of dietary arginine
https://watermark.silverchair.com/jamaoncology_szlosarek_202...
Prof Szlosarek reported grants from Barts Cancer Institute and Polaris Group and personal fees from Nestle Health Science (advisory board) during the conduct of the study. Dr Creelan reported grants from Iovance Biotherapeutics and SU2C/AACR; personal fees from Achilles Therapeutics, AstraZeneca, Regeneron, Hoffmann-La Roche, MJH Life Sciences, and ER Squibb LLC; and nonfinancial support from BMS and Clinigen outside the submitted work. Dr Taylor reported personal fees from AstraZeneca (speakers fees) outside the submitted work. Dr Grosso reported personal fees (advisory role) from MSD, BMS, Novartis, Novocure, and PharmaMar outside the submitted work. Dr Cortinovis reported personal fees (scientific adviser) from AstraZeneca, MSD, BMS, Roche, Sanofi Genzyme, Novartis, Amgen, and Seagen outside the submitted work. Dr Gilligan reported personal fees from AstraZeneca and Takeda outside the submitted work. Dr Kindler reported other from Polaris (payment to institution to support the clinical trial) during the conduct of the study; personal fees from AstraZeneca, Deciphera, Sanofi, Opna, Tempus, and Bluestar Genomics outside the submitted work. Dr Papadatos-Pastos reported personal fees from Takeda, MSD, Merck, AstraZeneca, Pfizer, and Amgen and travel support from Merck outside the submitted work. Dr Mansfield reported grants from Polaris Pharmaceuticals, Inc (payments to Mayo Clinic for conduct of clinical trial) during the conduct of the study; honoraria to Mayo Clinic from Sanofi Genzyme, Gilead, AbbVie, Immunocore, Roche, BeiGene, Janssen, and Bristol Myers Squibb Company, and serving on the board of directors (nonremunerated) for Mesothelioma Applied Research Foundation and Friends of Patan Hospital outside the submitted work. Dr Tsao reported personal fees from Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, EMD Serono, Genentech, GSK, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, Inc, and Summit Therapeutics outside the submitted work. Dr Nowak reported nonfinancial support from Douglas Pharmaceuticals and AstraZeneca outside the submitted work. Dr Bomalaski reported a patent for Polaris Pharmaceuticals licensed to Polaris. Dr Zauderer reported grants from Polaris to MSK during the conduct of the study; grants to MSK from MedImmune, GSK, Epizyme, Sellas Life Sciences, BMS, Takeda, Curis, and Atara and personal fees from Curis, Ikena, Takeda, GSK, Novocure; and personal fees and CME content from PER, Medscape, and Research to Practice outside the submitted work; and serving as Chair, Board of Directors, for Mesothelioma Applied Research Foundation (uncompensated). Dr Fennell reported grants from Astex Therapeutics, Bayer Oncology, Boehringer Ingelheim, BMS, Bergen Bio, Roche Oncology, and GSK; personal fees from AstraZeneca; and nonfinancial support from Clovis Oncology, Eli Lilly, and MSD outside the submitted work. No other disclosures were reported.
Prof Szlosarek reported grants from Barts Cancer Institute and Polaris Group and personal fees from Nestle Health Science (advisory board) during the conduct of the study. Dr Creelan reported grants from Iovance Biotherapeutics and SU2C/AACR; personal fees from Achilles Therapeutics, AstraZeneca, Regeneron, Hoffmann-La Roche, MJH Life Sciences, and ER Squibb LLC; and nonfinancial support from BMS and Clinigen outside the submitted work. Dr Taylor reported personal fees from AstraZeneca (speakers fees) outside the submitted work. Dr Grosso reported personal fees (advisory role) from MSD, BMS, Novartis, Novocure, and PharmaMar outside the submitted work. Dr Cortinovis reported personal fees (scientific adviser) from AstraZeneca, MSD, BMS, Roche, Sanofi Genzyme, Novartis, Amgen, and Seagen outside the submitted work. Dr Gilligan reported personal fees from AstraZeneca and Takeda outside the submitted work. Dr Kindler reported other from Polaris (payment to institution to support the clinical trial) during the conduct of the study; personal fees from AstraZeneca, Deciphera, Sanofi, Opna, Tempus, and Bluestar Genomics outside the submitted work. Dr Papadatos-Pastos reported personal fees from Takeda, MSD, Merck, AstraZeneca, Pfizer, and Amgen and travel support from Merck outside the submitted work. Dr Mansfield reported grants from Polaris Pharmaceuticals, Inc (payments to Mayo Clinic for conduct of clinical trial) during the conduct of the study; honoraria to Mayo Clinic from Sanofi Genzyme, Gilead, AbbVie, Immunocore, Roche, BeiGene, Janssen, and Bristol Myers Squibb Company, and serving on the board of directors (nonremunerated) for Mesothelioma Applied Research Foundation and Friends of Patan Hospital outside the submitted work. Dr Tsao reported personal fees from Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, EMD Serono, Genentech, GSK, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, Inc, and Summit Therapeutics outside the submitted work. Dr Nowak reported nonfinancial support from Douglas Pharmaceuticals and AstraZeneca outside the submitted work. Dr Bomalaski reported a patent for Polaris Pharmaceuticals licensed to Polaris. Dr Zauderer reported grants from Polaris to MSK during the conduct of the study; grants to MSK from MedImmune, GSK, Epizyme, Sellas Life Sciences, BMS, Takeda, Curis, and Atara and personal fees from Curis, Ikena, Takeda, GSK, Novocure; and personal fees and CME content from PER, Medscape, and Research to Practice outside the submitted work; and serving as Chair, Board of Directors, for Mesothelioma Applied Research Foundation (uncompensated). Dr Fennell reported grants from Astex Therapeutics, Bayer Oncology, Boehringer Ingelheim, BMS, Bergen Bio, Roche Oncology, and GSK; personal fees from AstraZeneca; and nonfinancial support from Clovis Oncology, Eli Lilly, and MSD outside the submitted work. No other disclosures were reported.