Poly Ligand Profiling differentiates pancreatic cancer patients according to treatment benefit from gemcitabine placebo versus gemcitabine evofosfamide and identifies candidate targets


Valeriy Domenyuk, Xianghua Liu, Daniel Magee, Zoran Gatalica, Adam Stark, Patrick Kennedy, Matthew Rosenow, Don Berry, George Poste,David Halbert, Charles Hart, Michael Famulok, Günter Mayer, Mark Miglarese, David Spetzler


The MAESTRO trial had randomized 693 locally advanced or metastatic pancreatic cancer patients to gemcitabine (G) + placebo vs G + evofosfamide (GE) and failed in phase III (OS hazard ratio (HR) 0.84, p=0.059). We hypothesized that clinical trial populations may include biomarker-defined subpopulations that benefit from the tested therapy. The accumulation of a multitude of subtle molecular aberrations during tumor progression limits the efficacy of anti-cancer drugs. A vast array of these variations can be assessed with Poly-Ligand Profiling (PLP), which is utilizing libraries of trillion unique single-stranded oligodeoxynucleotides (ssODNs) with aptameric binding properties. The aims of this study were to develop a PLP library that differentiates pancreatic cancer patients who can benefit (B) or not (NB) from GE or G therapy and identify the molecular targets of novel ligands.


  • Poly-Ligand Profiling (PLP) is a novel platform for classifying pancreatic cancer patients according to their benefit from GE treatment, which is based on aptameric properties of ssODN libraries.
  • The average simulated trial using data from all tumors increased the survival benefit to 116% of MAESTRO (average HR = 0.72), and 217% using only primary-site tumor (average HR = 0.63).
  • Demonstrated a novel approach for targets identification in FFPE tissue samples, pulled-down with enriched PLP library.
  • High-resolution MS of the PLP library pull-downs from gemcitabine non-benefiters cases reliably detected 20 proteins, 11 of which have reported association with pancreatic cancer and 6 of them are associated with gemcitabine resistance. 9 proteins are novel targets and require further evaluation.
  • In principle, the novel PLP platform could be applied to different therapeutic®imen for the development of urgently needed companion diagnostic tests in cancer and other diseases.

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