Benjamin A. Weinberg, MD

ABSTRACT: Colorectal cancer (CRC) is a commonly diagnosed malignancy. Although chemotherapy remains the backbone of treatment, the landscape of treating metastatic CRC (mCRC) is changing with the understanding of its heterogeneity and molecular blueprint. Colon cancer sidedness has proven to hold prognostic implications, with right-sided tumors having higher incidence of BRAF and KRAS mutations and being microsatellite instability–high (MSI-H); overall, they have a worse prognosis compared with left sided-tumors. Results of molecular research have demonstrated the need to profile each mCRC patient for RAS and BRAF mutations, MSI-H status, HER2 amplifications, and NTRK fusions. Ongoing clinical trials using targeted agents aim to further improve survival outcomes. We emphasize the epidemiology, knowledge of primary tumor location, and mutational landscape of mCRC, as well as novel treatment options for patients harboring unique subtypes of these characteristics.

Here we review drugs that target the EGFR and VEGF pathways, focusing on patient selection, drug toxicities, and how to choose agents for first-line therapy.

Here we review the evidence for use of biologic agents in the second-line setting and beyond. We also discuss off-label indications for biologics in selected patient populations, as well as biologics currently under development.

In this review, we address specific issues pertaining to AYA patients with colorectal cancer, including evaluation for hereditary colorectal cancer syndromes, clinicopathologic and biologic features unique to AYA patients with colorectal cancer, treatment outcomes, and survivorship.

This article reviews the current treatment paradigms for metastatic disease, focusing on ways to ameliorate symptoms and lengthen survival. We then summarize recent advances in our understanding of the molecular and cellular aspects of pancreatic cancer.