|Drug target||Cancer drugs||Company|
|VEGFR2||Ramucirumab||ImClone Systems Inc.|
|VEGF||Ziv-aflibercept||Sanofi and Regeneron|
VEGF, the first VEGF characterized, has served as a paradigm for the development of antiangiogenesis as a therapeutic strategy, including the clinical development of bevacizumab, a humanized monoclonal antibody targeting VEGF. In a pivotal trial, the use of bevacizumab in combination with irinotecan, 5-fluorouracil (5-FU), and leucovorin (IFL) was shown to improve the survival of patients with metastatic colorectal cancer (mCRC), resulting in its approval as the first antiangiogenic therapy. (Ref: Saif MW. Anti-VEGF agents in metastatic colorectal cancer (mCRC): are they all alike? Cancer Management and Research. 2013;5:103-115. ).
|Drug targets||Cancer drugs||Company|
|EGFR||Cetuximab||Bristol-Myers Squibb， Merck KGaA and Eli Lilly|
One of the most promising targeted therapies in colorectal cancer treatment involves the epidermal growth factor receptor (EGFR) which controls signaling pathways involved in cell differentiation, proliferation and angiogenesis. EGFR is expressed in 80% of colorectal cancers. It has been demonstrated that the anti-EGFR mAb cetuximab, alone or combined with irinotecan, improved responsiveness in patients with irinotecan-refractory colorectal cancer. Ras protein occupies a key position in the EGFR signaling pathway and activating K-Ras mutations are found in ∼30% of colon cancers. Several recent and concordant clinical studies conducted in colorectal cancer patients have shown that the presence of a K-Ras mutation is a significant predictor of resistance to anti-EGFR mAbs given alone or in combination with irinotecan in previously irinotecan-refractory patients. So far, possible relationships between K-Ras mutation status and EGFR status have not been investigated in colorectal cancer. (Ref: Milano G, Etienne-Grimaldi M C, Dahan L, et al. Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer[J]. Annals of oncology, 2008, 19(12): 2033-2038.)