Personalized Cancer Medicine Research Spearheaded by CureMatch Co-Founders

CureMatch Co-Founders Igor F. Tsigelny, Ph.D. and Razelle Kurzrock, M.D. along with colleagues from UC San Diego and University of Bergen have authored a personalized cancer medicine study examining activation of protein complexes utilizing an innovative 4D approach. “Proteins Flexibility as a Criterion for Elucidation of Activating Mutants” is a chapter in the book1 newly published by Springer to include the best presentations at the 6th International Conference on Simulation and Modeling Methodologies, Technologies and Applications.

This important study describes a new method for the prediction of a possible activating mutation in the binding region of two proteins leading to cancer development. This method is built on the concept that the binding process is not only based on the three-dimensional structure of binding proteins but also on the four-dimensional set of possible conformations adopted by means of the flexible regions of the involved proteins. The authors assert that a flexibility increase in the binding regions produced stronger binding energies and eventually lead to the possible increase of carcinogenicity of the protein complex. Doctors Sadakatsu Ikeda and Razelle Kurzrock used this theoretical finding for treatment of a cancer patient and achieved a significant improvement of his conditions.

Lead researcher, Dr. Igor Tsigelny, states, “Until now, only static information of mutations has been used to predict functional changes of proteins. We propose to move to the next level and add flexibility criteria for a 4D approach.”

It is imperative that personalized medicine clarify the functional effect of genomic variations at the protein level, decipher the molecular determinants of drug-specific sensitivity in tumors and, finally, predict the outcomes of patients treated by molecular-driven therapies. This study offers an approach to determining protein activity changes that occur due to these mutations using molecular dynamics (MD) simulations. The flexibility of binding sites in protein-protein complexes can be used to estimate the possible functional impact of mutations of amino acids located in these sites.

Researchers such as Tsigelny and Kurzrock are on the forefront of advances in intelligent systems and computing as applied to oncology. The implications of the molecular basis of cancer is extremely important to physicians making decisions on proper tumor treatment. Better cancer survival rates are the result of personalized medicine developments.

“Less than 20% of the papers submitted to the International Conference on Simulation and Modeling Methodologies, Technologies and Applications were selected for publication,” stated Stephane Richard Ph.D., CureMatch President and COO. “CureMatch is honored to have some of the world’s leading scientists and physicians as part of our team to establish standards for personalized cancer medicine.”

CureMatch is a digital health company which assists physicians with personalized treatment decisions. Actionable intelligence is generated via proprietary algorithms scouring evidence-based, custom-curated databases. The best Personalized Combination Therapy™ options are ranked for each individual patient by factoring proteomics and genomics information and scoring millions of potential combinations of cancer drugs in massive clinical and pharmacological knowledge databases.

Specific molecular alterations can be targeted with therapies uncovered by data-driven reports generated by CureMatch’s Decision Support System. Physicians recommend patient treatment plans based on the most current precision medicine. Improved outcomes are the result of matching treatments at the molecular level.

The study, “Proteins Flexibility as a Criterion for Elucidation of Activating Mutants” is authored by CureMatch co-founders Igor F. Tsigelny, Ph.D., San Diego Supercomputer Center, UCSD Moores Cancer Center and Department of Neurosciences and Razelle Kurzrock, M.D., UCSD Moores Cancer Center. Co-authors include Åge Aleksander Skjevik, Valentina L. Kouznetsova, Amélie Boichard, and Sadakatsu Ikeda.

The Advances in Intelligent Systems in Computing proceedings book reports on new and innovative solutions regarding methodologies and applications of modeling and simulation. It includes a set of selected, extended papers from the 6th International Conference on Simulation and Modeling Methodologies, Technologies and Applications (SIMULTECH), held in Lisbon, Portugal, from July 29-31, 2016. The conference brought together researchers, engineers and practitioners interested in methodologies and applications of modeling and simulation. SIMULTECH 2016 received 76 submissions from 35 countries and all continents. After a double-blind paper review performed by the Program Committee, 18% were accepted as full papers. A further selection was made after the conference, based also on the assessment of presentation quality and audience interest, so that the book includes the extended and revised versions of the very best papers from SIMULTECH 2016.

Book Reference

1 Springer International Publishing AG 2018

M.S. Obaidat et al. (eds.), Simulation and Modeling Methodologies, Technologies and Applications, Advances in Intelligent Systems and Computing 676,