"Cancer is a complex and heterogeneous disease driven by gene mutations. As we enter the era of personalized medicine, the characterization of the cancer genome has begun and will continue to influence diagnostic and therapeutic decisions in the clinic."
So begins Timothy Heffernan, Ph.D., associate director of target discovery at the Institute for Applied Cancer Science (IACS), in an article discussing how cancer genome discoveries have led to recent successes in oncology drug development through the identification of genetic alterations known as driver mutations.
"The translation of genomic data into drug development endpoints requires coordinated integration across multiple scientific disciplines. Genomic technologies provide comprehensive lists of genes that are altered in human cancer. Sophisticated computational models and powerful data analytics prioritize genes with the strongest weight of genomic evidence," he notes.
"Subsequent functional studies in relevant disease models provide biological significance by identifying genes that confer a proliferative and/or survival advantage to cancer cells. Lastly, deep biological exploration is required to provide a mechanistic understanding of the gene's cancer-relevant activity," Heffernan writes.
Systematic approaches to apply genomic data
Heffernan's article in the current issue of the Insights and Developments newsletter discusses the systematic approaches implemented at IACS to functionalize genomic data and identify novel therapeutic targets.
In a separate article Philip Jones, Ph.D., head of drug discovery at IACS continues his discussion, the second article of a three-part series, of key components in a successful drug discovery and development program, as well as the strategies that IACS has implemented to speed the delivery of innovative targeted therapies to patients.
In the inaugural issue of the newsletter Jones discussed the inherent challenges in translating scientific discoveries into effective therapies. Here he covers the critical role that target selection and validation contribute to program success.
Jones describes the rigorous target selection process that IACS employs, which considers, "(1) biologic relevance to tumorigenesis and general physiology; (2) tractability/technical feasibility of a drug discovery program; (3) clinical translatability (how a novel therapy would be used clinically); and (4) issues including competition, toxicity, freedom to operate and decision points."
Patient-centered drug discovery
Once a program is launched, an iterative workflow involving multiple disciplines commences. Because IACS is committed to delivering clinical candidates and not just tool compounds, Jones notes potential drugs must be "simultaneously optimized for multiple properties," including potency, pharmacokinetics and potential side effects.
IACS' approach is focused around three key tenets, which are: right target, right drug and right patients. In the final installment of this series, due out in June, Jones will address key aspects of translational research and clinical development. By connecting these three pillars, IACS and the broader MD Anderson community hope to address the critical need of patients for targeted and effective treatments.
Read about IACS projects to target resistant cancers and to develop immunotherapies in the latest issue of Conquest Magazine.