Complexity in the Gastric Cancer Genome and a Biomarker-Driven Trial of Poly (ADP-Ribose) Polymerase Inhibition in Gastric Cancer
Mené sur 124 patients atteints d'un cancer métastatique de l'estomac, cet essai randomisé de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout d'olaparib au paclitaxel en fonction du niveau de la protéine ATM
Gastric cancer remains a global health problem, with poor results from treatment in metastatic or recurrent disease and 723,000 deaths worldwide per year. Recent efforts at molecular classification of gastric cancer, including publication of the work of the Cancer Genome Atlas Network, have yielded insights into potential targets in the principal categories of Epstein-Barr virus–related, microsatellite unstable, genomically stable, and chromosomal unstable gastric cancer and confirm prior work on genetic and protein expression abnormalities in gastric cancer, among them alterations in the DNA damage response gene ataxia telangiectasia mutated (ATM). This expanded understanding of the importance of dysregulated DNA damage response has opened up the possibility of personalized application of synthetically lethal therapies that exploit these alterations in DNA damage response to foster apoptosis or mitotic catastrophe. In the article that accompanies this editorial, Bang et al have undertaken an admirable attempt at a biomarker-enriched trial to pursue this approach. The strengths and limitations of their trial are best understood in the context of the molecular subtypes of gastric cancer.
Journal of Clinical Oncology , éditorial en libre accès, 2015