J.Jpn. Surg. Soc.. 118(6): 639-645, 2017

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Feature topic

HOW WILL MOLECULAR-TARGETED THERAPIES AFFECT SURGICAL TREATMENT?

The clinical outcome of patients with metastatic colorectal cancer (mCRC) has improved greatly over the last 20 years. Multidrug chemotherapies combined with molecular-targeted agents have dramatically changed treatment strategies including conversion surgery. Improving clinical outcomes using molecular-targeted agents has attracted great interest. Patients receiving antiangiogenic molecules, such as anti-vascular endothelial growth factor-A (VEGF-A) and anti-VEGF receptor-2, a recombinant fusion protein containing VEGF-binding proteins and an oral multikinase inhibitor, have shown prolonged survival.
Past clinical trials showed that patients with RAS-wild mCRC derive benefit with evident tumor shrinkage from monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR). Both anti-VEGF-A mAbs and anti-EGFR mAbs are useful as first-line chemotherapy in RAS-wild mCRC, although which to select is still controversial. Some strategies based on the primary tumor location (right-sided/left-sided) or treatment goal (cytoreduction/disease control) were proposed in several guidelines. Better characterization of cancer genome complexity, such as the consensus molecular subtypes, may be useful for drug selection in the future. Understanding the medical effect mechanisms of molecular-targeted agents would benefit the patients of surgical oncologists.

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