Michael K. Gibson MD, PhD, discusses advancements in the identification of key biomarkers for patients with gastric or gastroesophageal junction adenocarcinoma, and the subsequent development of biomarker-driven therapeutics in this disease space.
Michael K. Gibson MD, PhD, research director, Translational Research in Head and Neck Oncology, Vanderbilt Health, associate professor of medicine, Vanderbilt-Ingram Cancer Center, discusses advancements in the identification of key biomarkers for patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, and the subsequent development of biomarker-driven therapeutics in this disease space.
Several decades of laboratory research has contributed to the identification of four key biomarkers expressed on the surface of tumor cells in adenocarcinoma, Gibson begins. These include HER2, Claudin 18.2, PD-L1, and FGFR2 alterations, he says.
HER2 was the first actionable target to be identified and targeted in gastric cancer following the read out of the phase 3 ToGA trial (NCT01041404) in 2010. This randomized controlled trial investigated the use of trastuzumab (Herceptin) in combination with chemotherapy vs chemotherapy alone as a first-line treatment for HER2-positive, gastric/GEJ adenocarcinoma. Results from this trial showed that the experimental regimen was highly effective in this patient population, and have supported subsequent use of HER2-targeted options in this space.
Improved molecular characterization of gastric cancer has allowed for the identification of the remaining 3 biomarkers. Claudin 18.2, PD-L1, and FGFR2 mutations or alterations are considered more practical and emerging targets for therapeutic development, Gibson continues.
Currently, there is a significant need for the incorporation of targeted approaches in clinical practice for adenocarcinoma aside from first-line anti-HER2 therapy and second-line anti-VEGF therapy. Targeting these alterations may confer a higher degree of benefit for patients with adenocarcinoma, thereby improving patient outcomes, he explains. Moreover, the ability to identify more viable cell-surface markers of this disease and potentially develop novel monoclonal antibodies to target them may result in a shift in the treatment landscape, Gibson concludes.