Cellular Metabolism Case Study

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AGIOS – THE OTHER SIDE OF THE POSSIBLE
Company Overview:
Agios is a biopharmaceutical company headquartered in Cambridge, MA, United States of America. It is a coming together of dedicated professionals who are passionately committed to application of their scientific capabilities and leadership in the field of cellular metabolism to confront the problems posed by the cancer. The company’s motto is to help in transforming the lives of cancer patients and patients with rare genetic metabolic disorders which are a subset of orphan genetic metabolic diseases. The company believes it is a pioneer in using cellular metabolism. Cellular metabolism has been a unexploited area in cancer research before a stream of companies led by Agios started foraying
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It is the new and exciting field of research that could provide a novel approach to treating cancer. Cancer cells tend to become addicted to particular fuel sources and alter their metabolism. The altered metabolism of the cancer cell could provide a novel intervention point for developing novel targeted cancer drug. This alteration of metabolism in cancer cells is called as metabolic rewiring. The metabolic rewiring is the result of genetic and genomic alterations in oncogenes( genes that transform normal cells into tumor cells) and tumor suppressor genes (genes that are antioncogenetic) which are responsible for cell signaling. Recent research shows a possibility that these altered metabolic pathways fundamentally drive tumor growth rather than being just a result of cancer. The development of cancer metabolism inhibitors and the possibility combining them with other cancer therapies in vogue could have a profound impact on cancer…show more content…
IDH is a cytosolic enzyme which occurs in three isoforms. The enzyme catalyses the oxidative decarboxylation of Isocitrate producing alpha-ketoglutaric acid and carbon dioxide. This step of citric acid cycle is an irreversible step and hence it is carefully regulated to avoid unnecessary depletion of isocitrate. Specific mutations of IDH1 and IDH2 have been found in many cancer cells such as gliomal cancers, astrocytomas and acute myeloid leukemia (AML). These mutations produce (D)-2- hydroxyglutarate from alpha-ketoglutarate. (D)- 2- Hydroxyglutarate which accumulates in cytosol. This leads to inhibitions of several enzymes dependant on alpha-ketoglutaric acid. The whole process results in hypermethylation of DNA and histones. The hypermethylation can activate oncogenes and suppress tumor suppressor genes. The company reckons that inhibition of these mutated IDH may lead to clinical benefit for those patients with cancers which are carrying mutated IDH. The efforts of research and development of company is directed towards developing lead drug candidates called as IDH

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