Identifying Potential Targets for Companion Diagnostic Tests Using Poly-Ligand Profiling

Researchers identified potential targets for a companion diagnostic tests using poly-ligand profiling (PLP) to determine which patients with locally advanced or metastatic pancreatic cancer may benefit from gemcitabine plus evofosfamide. Their findings suggest that patients with shorter overall survival (OS) were more likely to express proteins associated with gemcitabine resistance, according to a study presented at the ESMO World Congress on Gastrointestinal Cancer 2018.¹

PLP uses libraries of a trillion single-stranded DNA sequences with aptamer binding properties to detect genetic variants that may be associated with response or lack of response to treatment. The purpose of this study was to develop a PLP library that identifies patients with advanced pancreatic cancer who are likely to respond to gemcitabine plus evofosfamide.

The study used tissue specimens from the phase 3 MAESTRO trial for a training set and a blinded set. The blinded set was used to assess performance to estimate the effect on the MAESTRO study through simulations. The PLP-enriched library was developed using patients with good versus poor OS outcomes. Mass spectrometry was used to identify the proteins detected by PLP.

The simulations of the PLP-positive patients demonstrated a longer OS among patients who received gemcitabine plus evofosfamide compared with placebo (hazard ratio, 0.72).

After using the PLP library, mass spectrometry detected a total of 20 proteins. Eleven of the proteins have previously been associated with pancreatic cancer and 6 have been correlated with gemcitabine resistance, including vimentin, pyruvate kinase, endoplasmic reticulum chaperone BiP, heat shock protein HSP 90-alpha, histone H3-1, and heat shock protein beta-1.

The authors concluded that the study found potential targets associated with resistance to gemcitabine. They noted that “the novel PLP platform could be applied to different therapeutic regimens for the development of urgently needed companion diagnostic tests in cancer and other diseases.”

Read more of Cancer Therapy Advisor‘s coverage of the ESMO World Congress on Gastrointestinal Cancer 2018 meeting by visiting the conference page.

Reference

1. Domenyuk V, Liu X, Magee D, et al. Poly-ligand profiling differentiates pancreatic cancer patients according to treatment benefit from gemcitabine+placebo versus gemcitabine+evofosfamide and identifies candidate targets. Ann Oncol. 2018;29 (suppl 5;abstr P-132):v36. doi: 10.1093/annonc/mdy151.131