Epidermal growth factor receptor inhibitors in oncology Journal Article
| Authors: | Vivanco, I.; Mellinghoff, I. K. |
| Article Title: | Epidermal growth factor receptor inhibitors in oncology |
| Abstract: | Purpose of review: Inhibition of the epidermal growth factor receptor (EGFR) by small molecules or antibodies has been pursued as a paradigm to treat human cancers for over two decades. It is now clear that these agents can induce tumor regressions in a variety of human cancers, proving the critical role of EGFR signals for tumor maintenance in subsets of patients with these cancers. Clinically meaningful responses, however, are only transient and further refinement of EGFR-targeted therapies is urgently needed. Recent findings: Several studies provide new insights into the molecular basis of EGFR kinase inhibitor resistance, including co-activation of the MET growth factor receptor, loss of the phosphatase and tensin homolog (PTEN) tumor suppressor, and KRAS mutation. Potential strategies are emerging to overcome acquired EGFR kinase inhibitor resistance associated with the T790 M EGFR mutation, including a new compound identified in a chemical library screen and a combination regimen of an anti-EGFR antibody plus a small molecule EGFR kinase inhibitor. Lastly, pulsatile dosing schedules are being pursued to accomplish more complete target inhibition. Summary: Current data point toward a strong association between EGFR genotype and EGFR kinase inhibitor response, similar to the findings with other oncogenic kinases (BCR-ABL, HER2, KIT, PDGFRA, BRAF). This relationship is less obvious for antibodies targeting EGFR. More complete inhibition of EGFR in tumor cells and more focused clinical drug development remain important goals toward further success with this class of anticancer agents. © 2010 Wolters Kluwer Health | Lippincott Williams and Wilkins. |
| Keywords: | unclassified drug; gene mutation; review; erlotinib; nonhuman; capecitabine; gemcitabine; pancreas cancer; neoplasms; colorectal cancer; animals; breast cancer; lung non small cell cancer; receptor, epidermal growth factor; cetuximab; irinotecan; monoclonal antibody; panitumumab; pf 299804; protein kinase inhibitors; drug mechanism; glioblastoma; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; clinical evaluation; gefitinib; down regulation; gene inactivation; letrozole; k ras protein; b raf kinase; lapatinib; epidermal growth factor receptor kinase inhibitor; drug indication; matuzumab; zalutumumab; kinase inhibitor; 4 [3 chloro 4 (2 pyridinylmethoxy)anilino] 3 cyano 6 (4 dimethylaminocrotonamido) 7 ethoxyquinoline; epidermal growth factor receptor addiction; gatekeeper mutation; canertinib; ch 806; imc 11 f8; n [4 (3 chloro 4 fluoroanilino) 7 (tetrahydro 3 furyloxy) 6 quinazolinyl] 4 dimethylamino 2 butenamide; nimotuzumab; wz 4002; xl 647 |
| Journal Title: | Current Opinion in Oncology |
| Volume: | 22 |
| Issue: | 6 |
| ISSN: | 1040-8746 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2010-11-01 |
| Start Page: | 573 |
| End Page: | 578 |
| Language: | English |
| DOI: | 10.1097/CCO.0b013e32833edbdf |
| PUBMED: | 20739887 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CUOOE" - "Source: Scopus" |
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