Multiplatform tumor profiling identifies options for patients with TKI-resistant gastrointestinal stromal tumors

Jan. 16, 2015

Caris Life Sciences recently announced the presentation of data from a study in which Caris Molecular Intelligence, the company’s panomic, comprehensive tumor profiling service, identified potential therapeutic options for patients with gastrointestinal stromal tumors (GIST) that are resistant to standard tyrosine kinase inhibitor (TKI) therapy. Presented at the 2015 Gastrointestinal Cancers Symposium in San Francisco, the data suggest that various cytotoxic chemotherapeutics and novel targeted agents may be viable treatment options for patients with GIST, due to these agents’ apparent ability to circumvent TKI resistance mechanisms.

Using Caris Molecular Intelligence, researchers employed a multiplatform approach that included a combination of gene sequencing (Sanger and next-generation sequencing), protein expression (immunohistochemistry), and gene amplification (in situ hybridization) to evaluate biomarkers in 147 GIST cases. They identified a multidrug resistance phenotype (P-glycoprotein) and/or multidrug resistance protein 1 [MRP1]) in 52 percent to 68 percent of patients. They also observed a high frequency (72 percent) of low tubulin beta 3 (TUBB3) expression in the studied cases, suggesting that tubulin-binding agents such as taxanes or vinca alkaloids may be of potential use in patients with GIST.

According to the investigators, as many as one-third of patients with GIST may benefit from anthracyclines and topoisomerase inhibitors, based on the expression patterns of topoisomerases 1 (TOPO1, 34 percent) and 2A (TOPO2A, 32 percent). Due to the high frequency of low expression of the DNA repair genes MGMT (47 percent), thymidylate synthase (TS, 70 percent), and RRMI1 (79 percent), the investigators concluded that cytotoxic agents used in non-GIST solid tumors should strongly be considered as an alternative therapy for GIST once TKIs fail and/or for GIST that are cKIT and PDGFRA wild type.

Learn more on the Caris website