Scott Kopetz

Scott Kopetz is a leader in the molecular oncology and precision medicine of colorectal cancer (CRC), with international recognition for his work on BRAF-mutant and KRAS-mutant CRC. As Professor and Deputy Chair for Translational Research in the Department of Gastrointestinal Medical Oncology at MD Anderson Cancer Center, his research integrates genomic profiling, biomarker-driven clinical trials, and circulating tumor DNA to reshape the therapeutic landscape of metastatic CRC. Kopetz is best known as the principal investigator of the BEACON CRC trial, a landmark randomized phase III study that established the combination of encorafenib (BRAF inhibitor) plus cetuximab (anti-EGFR antibody) as a new standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer — a historically poor-prognosis subgroup comprising approximately 8–10% of mCRC patients. The BEACON study demonstrated a doubling of overall survival compared to standard chemotherapy and led to FDA approval of the encorafenib-cetuximab regimen in 2020. It also validated the critical concept that BRAF inhibition in CRC must be coupled with EGFR blockade to prevent adaptive feedback reactivation of the MAPK pathway. Beyond BRAF, Kopetz has been a leading clinical investigator in the emerging field of KRAS G12C inhibitors in colorectal cancer. He led early studies demonstrating that sotorasib and adagrasib have activity in KRAS G12C-mutant CRC, and that combination strategies — particularly with anti-EGFR antibodies — substantially improve response rates by overcoming EGFR-mediated adaptive resistance. His work on the KRYSTAL-1 and CodeBreaK trials has informed regulatory approvals and combination regimen development for this previously undruggable target. Kopetz's laboratory has also made major contributions to ctDNA biomarker development in CRC. His group demonstrated that ctDNA clearance at early treatment timepoints predicts response and survival in metastatic CRC, and that ctDNA-based minimal residual disease (MRD) detection after surgery for early-stage CRC identifies patients at high risk for relapse who may benefit from adjuvant chemotherapy. These insights are being prospectively validated in the CIRCULATE-US trial. Kopetz is the author of over 400 peer-reviewed publications and is widely regarded as one of the most productive and influential clinical translational investigators in colorectal oncology.

Scott Kopetz 是结直肠癌分子肿瘤学和精准医学领域的领军人物，以其在BRAF突变和KRAS突变结直肠癌方面的工作享誉国际。他是BEACON CRC试验的首席研究员，该里程碑式的III期随机研究确立了encorafenib联合cetuximab作为BRAF V600E突变转移性结直肠癌的新标准治疗方案，并于2020年获FDA批准。 Kopetz 在KRAS G12C抑制剂领域领导了早期临床研究，证明联合抗EGFR抗体可显著提高应答率。他在ctDNA生物标志物方面的研究证明ctDNA清除可预测治疗反应，微小残留病灶检测可识别高复发风险患者。