Oss, October, 11th, 2017 – A high-throughput screening approach to identify novel synergistic drug combinations has been launched by NTRC under the name SynergyScreen™. The new service product is available as an extension to NTRC’s cell line profiling on the 102 cancer cell line Oncolines™ panel.

SynergyScreen™

The aim of combination drug treatment in cancer therapy is to improve response rate and to decrease the probability of the development of drug resistance. The discovery of new effective drug combinations is constrained by the cost and effort of carrying out large unbiased screens. NTRC scientists have previously shown [1] that curve shift analysis by the approach developed by Straetemans et al. [2] is a more robust method of determining synergy than combination matrix screening using Bliss-scoring. In addition, it shown that NTRC’s workflow for single agent cellular IC50 determination is highly reproducible compared to other workflows [3]. To bring these advantages to bear, and to increase the throughput of identifying new synergistic drug combinations, a two-step approach consisting of screening and confirmation was developed at NTRC.

Combination of PARP inhibitor and topoisomerase inhibitor irinotecan studied by SynergyScreen™ (left) and SynergyFinder™ (right).

NTRC at Molecular Targets and Cancer Therapeutics conference

The screening approach will be presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference, to be held in Philadelphia (USA) from October 27th to 30th. Results will be presented of a SynergyScreen™ with a poly-ADP ribose polymerase (PARP) inhibitor, the BET bromodomain inhibitor JQ1 and inhibitors of the spindle assembly checkpoint.

The poster on SynergyScreen™ will be presented by Dr. Suzanne van Gerwen on Saturday, October 28th, p.m.

Title: Novel synergistic drug combinations of PARP, bromodomain, and spindle assembly checkpoint kinase inhibitors by large-scale screen of 150 anticancer agents

Session Title:                                   Poster Session A

Session Category:                           Drug Screening

Session Date and Time:                  Saturday Oct 28, 2017 12:30 PM – 4:00 PM

Location:                                          Hall E, Pennsylvania Convention Center

Poster Board Number:                    153

Permanent Abstract Number:          A153

Meet NTRC Services at booth #815 in the Exhibition Hall of the Pennsylvania Convention Center

Literature references:

[1] Uitdehaag et al. (2015) Selective targeting of CTNNB1-, KRAS- or MYC-driven tumor cell growth by combinations of existing drugs. PLoS ONE 10(5): e0125021.

[2] Straetemans et al. (2005) Design and analysis of drug combination experiments. Biometrical Journal 47, 299-308.

[3] Uitdehaag et al. (2016) Cell panel profiling reveals conserved therapeutic clusters and differentiates the mechanism of action of different PI3K/mTOR, Aurora kinase and EZH2 inhibitors. Molecular Cancer Therapeutics 15, 3097-3109.

About NTRC

NTRC is a precision medicine company dedicated to the development of new anti-cancer drugs. NTRC facilitates the development of novel therapies by providing cancer cell line profiling services (Oncolines™, OncolinesProfiler™, SynergyFinder™ and SynergyScreen™) and target residence time measurements for protein kinases (ResidenceTimer™) on a fee-for-service basis. NFK GreenScreen™, an assay read-out for the cancer immunotherapy drug targets IDO1 and TDO, is supplied to clients globally. NTRC has internal drug discovery programs on TTK, IDO1 and TDO. For more information please visit www.ntrc.nl or contact [email protected]