Unlike breast or lung cancer where a biomarker's effectiveness persists across treatment stages, biomarkers in upper GI cancers often fail to show similar efficacy when moved from one line of therapy to another. This suggests a more variable and rapidly changing tumor biology.
For BRAF V600E mutated colorectal cancer, data argues against the common practice of starting with chemotherapy and saving targeted therapy for later. Hitting the specific tumor biology hard and early with combination targeted agents leads to significantly better outcomes, including doubling overall survival.
While re-biopsying at disease progression is the "by-the-book" standard to confirm biomarkers like HER2, clinicians acknowledge it is often skipped. The difficulty of obtaining tissue and the desire to provide patients with potential treatment options create a gap between guidelines and clinical reality.
Contrary to concerns about over-complicating treatment, experts advocate for fragmenting gastric cancer even further. The goal is to treat each molecularly defined subset as its own distinct disease, which requires deeper understanding and more targeted approaches rather than broad simplification.
A key future goal in GI oncology is for systemic drugs to become so effective in early disease stages that they diminish or eliminate the need for surgery and radiation. This would spare patients from life-changing procedures like organ removal for gastric, rectal, and pancreatic cancers.