About nine out of 10 new cancer drugs successfully clear preclinical development hurdles, but then they fail in human clinical testing. A new partnership facilitated by SAIC-Frederick Inc. aims to help change that outcome.
The partnership brings together The UC Davis Cancer Center, The Jackson Laboratory and the National Cancer Institute's (NCI) Center for Advanced Preclinical Research (CAPR), all under the umbrella of NCI's Advanced Technology Partnerships Initiative (ATPI). SAIC-Frederick facilitates translational research and development partnerships in cancer and AIDS for the ATPI as part of its longstanding operations and technical support contract with NCI.
Under the partnership, a range of genetically engineered and human transplant mouse model studies will be integrated with patient treatment clinical trial studies under a uniform and controlled testing mechanism. Data resulting from this combined approach will help identify molecules (biomarkers) that could predict conditions under which candidate drugs will be most effective. These data could be invaluable for designing clinical trials and improving treatment outcomes.
The new approach has been named the iGXT Platform™ — for integrated genetically engineered mouse models (GEMMs)/patient-derived tumor Xenograft models (PDXs)/clinical Trials.
The partnership draws on particular strengths of each organization. The Center for Advanced Preclinical Research (CAPR) brings expertise in engineered mouse models. The Jackson Laboratory adds experience in human transplant models, and UC Davis contributes extensive knowledge of cancer drug clinical trials and laboratory resources.
NCI's work under the platform will be conducted at the Center for Advanced Preclinical Research (CAPR) in Frederick, Md. NCI-Frederick is a government-owned, contract-operated federal national laboratory with SAIC-Frederick as prime contractor.
The iGXT Platform™ was presented at the ASCO Annual Meeting in Chicago on June 6, and will be presented at the World Conference on Lung Cancer in Amsterdam on July 6.
Data to be presented at the conferences will provide insights into the transition from empiric to rationally selected and personalized therapy utilizing the platform. The iGXT Platform is currently being employed in studies of Non-Small Cell Lung Cancer (NSCLC) involving Epidermal Growth Factor Receptor (EGFR)-directed therapies, mutation-specific GEMM and PDX models, and in conjunction with genome-wide assessment of altered gene expression and other molecular changes, pre-and post-therapy.
Future plans are for the platform to expand into brain cancers, ovarian cancer, prostate cancer and melanoma.
Specific studies are currently being conducted in collaboration with pharmaceutical companies and others in the biomedical research community. Organizations are encouraged to inquire about access to the platform for specific studies, and for models and materials that are available through the Center for Advanced Preclinical Research and Jackson Laboratory programs.
"There is an urgent need for more predictive models of human cancer for drug discovery," said Chuck Hewett, Ph.D., Executive Vice President and COO of The Jackson Laboratory. "Unfortunately, nine out of 10 cancer drugs entering preclinical testing fail. This comes at great cost to the pharmaceutical industry and to patients. The integrated approach we have with CAPR and UC Davis targets these issues directly."
David Hoekzema, Vice President for Business Development at SAIC-Frederick, said, "Knowledge of the genetic basis of human cancers can be combined with advanced genetic engineering techniques to produce lab animals that mimic the diseases in humans more accurately than traditional experimental mouse models. By integrating CAPR's expertise in this area with the unique capabilities of JAX, and into the clinical environment of UC Davis, we have a unique approach with great potential to significantly impact the traditional drug development paradigm."
David Gandara, MD, Professor of Medicine, Division of Hematology and Oncology, Associate Director of Clinical Research for UCDCC, and Principal Investigator presenting on the iGXT Platform™ presentation at ASCO, said, "This new research platform is designed to utilize unique strengths of the three partners to improve our understanding of why some cancer patients, who may look similar clinically, have such different results when treated with the same cancer treatments, and to optimize the therapeutic options for each individual patient. We anticipate that this approach will accelerate the move toward personalized cancer therapy."
About the Center for Advanced Preclinical Research: The NCI CAPR program is headed by Dr. Terry Van Dyke, Chief, Mouse Cancer Genetics Program and Director, CAPR. CAPR has a cancer translational research-centered mission to facilitate the contribution of genetically engineered mouse models (GEMMs) and other relevant mouse cancer models to the improvement in overall preclinical drug development systems, including improvements to the process of selecting novel therapeutics for clinical trials and developing relevant biomarkers for treatment selection and evaluation. The CAPR mission includes the strategy development for predictive preclinical research with the aim to facilitate their routine application in clinical research in order to achieve optimal outcomes in the management of cancer diseases. CAPR achieves its mission through internal projects focused on applied preclinical development and via extensive collaborative partnerships (both private and public) with a focus on therapeutics and biomarker development.
About The Jackson Laboratory: The Jackson Laboratory is a nonprofit genetics research institution founded in 1929 to study the genetic basis of preventing, treating and curing disease, with a particular emphasis on cancer. It has been a National Cancer Institute-designated Cancer Center since 1983 and its resources and research principles are associated with 22 Nobel Prizes. With a current operating budget of $200 million, JAX employs about 1,300 people, including 38 principal investigators leading research in cancer, aging, immunology, neurology, metabolic disorders, reproduction, computational biology and more.
About UC Davis Cancer Center: UC Davis Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its top specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and offer patients access to more than 150 clinical trials at any given time. Its innovative research program includes 188 physicians and scientists at UC Davis and Lawrence Livermore National Laboratory. The unique partnership, the first between a major cancer center and national laboratory, has resulted in the discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis is collaborating with a number of hospitals and clinical centers throughout the Central Valley and Northern California area to offer the latest cancer care services. The Center actively explores, develops, and facilitates the translation of research into new detection, treatment, and prevention strategies. One of the premier clinical research platforms at UCDCC is the NCI-sponsored N01 award for early therapeutic drug development, a centerpiece for the current iGXT collaboration.