Current synthetic pharmacotherapy for treatment-resistant colorectal cancer: when urgent action is required

Colorectal cancer (CRC) remains a global concern. Fourteen antineoplastics are approved for metastatic CRC (mCRC); however, the 5-year overall survival remains poor for the overwhelming majority of patients. Poor outcomes continue to highlight the critical need for therapeutic advancement. Areas covered: mCRC represents a clinical and molecular complex malignancy with several treatment barriers. Prognostic and predictive factors have and continue to emerge anatomically, molecularly, and via patient-related factors. Herein, the authors review the current understanding and promising future directions amongst these different subtypes. Expert opinion: CRC is largely considered a common cancer. Consequently, treatment approaches have been rather homogenous with systemic chemotherapy combinations. Of significance is the recent identification of targetable rare subsets of mCRC, notably for microsatellite instability-high (MSI-H) patients and for BRAF mutated patients. As a result, we are at the forefront of interpreting biological differences that provide targetable approaches and/or additional insight. To continue to do so, future clinical trial developments must focus on diverse subtypes of mCRC rather than all-encompassing mCRC proposals. Yet of greatest need is identifying options for RAS-mutated and microsatellite-stable mCRC patients. For the majority of these patients, we continue to seek novel innovative approaches to improve the overall survival of these patients.