KRAS is downstream of EGFR, and hence patients who already have activating mutations in KRAS would not benefit from such therapy. Patients who are not responsive to first-line chemotherapeutic drugs and whose KRAS status is wildtype are sometimes offered anti-epidermal growth factor receptor (anti-EGFR) therapy such as Cetuximab and Panitumumab. Despite better median survival in responders in the past two decades, respond rate to chemotherapy remained stagnant. Current chemotherapeutic drugs for advanced CRC have a dismayed success rate of less than 30%. Colorectal cancer (CRC) is the third most frequent cancer and a leading cause of cancer mortality worldwide, attributable mainly to metastasis to distal organs such as liver and lung. Thus, a substantial number of intracellular targets remain untargeted, which opens potential therapeutic opportunities.Ĭancer is a major debilitating disease ( ). Most of these targets are predicted to be membrane proteins (59%), and 16% are secreted. Food and Drug Administration has approved drugs targeting human proteins from 618 genes, in which 535 proteins are targeted by synthetic small molecule inhibitors (SMIs) and only 108 are targeted by biologics. Most (74%) of the genes strongly implicated in cancer by COSMIC encoded intracellular proteins which primarily localized to the cytosol or nucleoplasm.
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