Much of the current focus in cancer research is on studying cancer driver genes. In search for new and effective cancer drugs, this has been translated into searching for ‘actionable’ mutations in these genes, aiming at their therapeutic targeting. However, identifying novel genetic interactions occurring between cancer genes may open new drug treatment opportunities across the whole cancer genome.
This workshop will focus on a new approach that have been developed for the datadriven identification of the synthetic lethal interactions by directly mining patients’ tumor data. Applying it to analyze the Cancer Genome Atlas (TCGA) data, the Ruppin lab identified first pan-cancer genetic interaction networks shared across many types of cancer, which was then validated via existing and new experimental in vitro and in vivo screens.
Synthetic lethal interactions offer an exciting route for personalized selective anticancer treatments enabling the prediction of patients’ drug response and identification of new selective drug target candidates.
Attendees will learn:
Joo Sang lee, Research Fellow Cancer Data Science Lab National Cancer Institute , National Institute of Health
Joo Sang Lee is a senior member of the newly established Cancer Data Science Lab at NCI/NIH. In this position, Joo leads the research on harnessing genetic interactions, with emphasis on synthetic lethality, to advance precision cancer medicine. His research studies the applications of synthetic lethality to identify biomarkers and stratify patients for therapy, and for identifying novel combinations for both targeted and immunotherapies.
Development of suitable screening tools has the potential to facilitate the identification of DNA repair inhibitors and mapping genetic interactions between pathways. In this workshop attendees can learn from this case study how synthetic lethal interactions were uncovered:
Ranjit Bindra, Co-Founder , Cybrexa Therapeutics
Dr. Ranjit Bindra is a physician-scientist at the Yale School of Medicine. Clinically, he treats adult and pediatric primary CNS tumors. In the laboratory, his group recently led a team of four major laboratories at Yale. As a biotech entrepreneur, Dr. Bindra has started several life sciences ventures over the last 10 years. Most recently, he co-founded Cybrexa Therapeutics, a Series B round-funded company focused on developing an entirely new class of small molecule DNA repair inhibitors, which directly target the tumor microenvironment.
which reported the stunning discovery that IDH1/2-mutant tumors harbor a profound DNA repair defect that renders them exquisitely sensitive to PARP inhibitors. This work was published in Science Translational Medicine, and it has received international attention with major clinical implications. Building on this discovery, a more recent study in his laboratory was published in Nature Genetics, which highlights the expanding significance of this work: specific tumor-associated mutations induce the aberrant production of citric acid cycle-related metabolites, which drives genetic instability and BRCAness. Dr. Bindra is now translating this work directly into patients, in four phase I/II clinical trials, including an innovative, biomarker-driven trial specifically targeting the Adolescent/Young Adult (AYA) cancer patient population. In addition, he is lead co-PI of a 35-site, NCI-sponsored Phase II trial testing the PARP inhibitor, olaparib, in adult IDH1/2-mutant solid tumors (NCT03212274).
As a biotech entrepreneur, Dr. Bindra has started several life sciences ventures over the last 10 years. Most recently, he co-founded Cybrexa Therapeutics, a Series B round-funded company focused on developing an entirely new class of small molecule DNA repair inhibitors, which directly target the tumor microenvironment. This approach leverages a novel tumor-localizing peptide technology developed by an internationally recognized research laboratory at Yale. Cybrexa is led by an experienced business team that has built numerous successful biotech ventures and raised hundreds of millions of dollars in venture capital.
Dr. Bindra received his undergraduate degree in Molecular Biophysics and Biochemistry from Yale University in 1998, and both his MD and PhD from the Yale School of Medicine in 2007. He completed his medical internship, radiation oncology residency, and post-doctoral research studies at the Memorial Sloan-Kettering Cancer Center in 2012.