Amakye D.,Novartis |
Jagani Z.,Novartis |
Dorsch M.,Agios Pharmaceuticals
Nature Medicine | Year: 2013
Major progress has been made in recent years in the development of Hedgehog (Hh) pathway inhibitors for the treatment of patients with cancer. Promising clinical trial results have been obtained in cancers that harbor activating mutations of the Hh pathway, such as basal cell carcinoma and medulloblastoma. However, for many cancers, in which Hh ligand overexpression is thought to drive tumor growth, results have been disappointing. Here we review the preclinical data that continue to shape our understanding of the Hh pathway in tumorigenesis and the emerging clinical experience with smoothened inhibitors. © 2013 Nature America, Inc.
Berardi M.J.,Harvard University |
Fantin V.R.,Agios Pharmaceuticals
Current Opinion in Genetics and Development | Year: 2011
Malignant transformation is often a multistep process characterized by an initial period of avascular growth. Rapid cell proliferation creates areas within the emerging preneoplastic lesion with limited diffusion of oxygen and nutrients. In this context, activation of oncogenes, loss of tumor suppressors as well as additional adaptive mechanisms drive a profound metabolic rewiring to overcome the environmental constraints. The emerging cells are in principle better suited to proliferate and survive in the hostile tumor microenvironment. Furthermore, some of the acquired metabolic traits impact their metastatic behavior and response to therapy. It is becoming increasingly clear that malignant cells are highly dependent on certain nutrients, an Achilles' heel of cancer and an opportunity for therapeutic intervention. © 2010.
Agios Pharmaceuticals | Date: 2015-07-31
Compounds of general formula I: and compositions comprising compounds of general formula I that modulate pyruvate kinase are described herein. Also described herein are methods of using the compounds that modulate pyruvate kinase in the treatment of diseases.
Agios Pharmaceuticals | Date: 2015-09-28
Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).
Agios Pharmaceuticals | Date: 2014-03-13
Compounds of general formula (I) and compositions comprising compounds of general formula (I) that modulate pyruvate kinase are described herein. Also described herein are methods of using the compounds that modulate pyruvate kinase in the treatment of diseases.