Large- and small-molecule inhibitors of transforming growth factor-beta signaling.
A variety of drugs have been developed to inhibit transforming growth factor (TGF)beta signaling. These drugs have been designed to block TGFbeta synthesis, ligand/receptor binding or receptor kinase signaling. Preclinical studies using TGFbeta inhibitors have demonstrated efficacy in reducing metastasis and have shown improvements in cytotoxic drug delivery. Results of phase I/II clinical trials of TGFbeta inhibitors in patients with glioblastoma suggest improved survival rates compared with conventional chemotherapy. The predominant cellular target, whether cancer or stromal cell, immune cell or angiogenesis, may differ between tumor types. Different individuals may show variable responses to drug therapy dependent on both germline genetic variation and the somatic mutation profile of the tumor. A deeper understanding of these issues will assist in targeting the right patients for such therapy, and in limiting unwanted side effects.
Akhurst
Rosemary J
RJ
University of California at San Francisco, P.O. Box 0875, Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94143-0875, USA. rakhurst@cc.ucsf.edu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use; D018579:Patient Selection; D011621:Pteridines / Q000494:pharmacology / Q000627:therapeutic use*; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D011621:Pteridines; D018125:Receptors, Transforming Growth Factor beta; C511004:SD-208; D016212:Transforming Growth Factor beta; C475848:Lerdelimumab