Tumor Slice Culture: A New Avatar in Personalized Oncology
Abstract
Cancer of the large intestine (colon and rectum) ranks the third most common and second most deadly in the United States. It affects Service members and their families as much as the civilian population. Sadly, approximately half of these patients develop metastatic disease (i.e., spread), most frequently to the liver, resulting in premature deaths. Scientific advances have led to a much better appreciation of the genetic changes (e.g., mutations) associated with the development and progression of colorectal cancer (CRC). Like most cancers, CRCs differ from one another in their genetic make-up, clinical behavior, and treatment response. This holds true even within one tumor, which makes it challenging for physicians to choose the best treatment for individual patients. Despite the promise of personalized medicine to define the precise genetic landscape of each cancer, there remains an enormous gap between our knowledge of the genomic alterations harbored by a tumor and how these changes affect the biology of the cancer and its response to drugs. In other words, there is a missing link between the scientific world of cancer genetics and the clinical world of therapeutic decisions. The outdated "one-size-fits-all" paradigm of prescribing chemotherapy according to conventional diagnosis must be abandoned. To bring us closer towards the goal of tailoring "effective" therapy for individual cancer (i.e., "personalized" oncology), we will establish a new platform for testing drug sensitivity outside the body, using tissues directly obtained from the patient s cancer in the form of a slice culture. Pieces of human cancers will be kept alive in an incubator for days without significant detriment to their viability. During this period, we will test a variety of drugs and cell-based therapies to determine their effects on the specific tumors. Unlike other forms of human cancer models, our Tumor Slice Culture (TSC) system utilizes a standardized easy-to-follow protocol to come up with results that are reproducible and clinically relevant in a very short timeframe compared to other methods (e.g., 2 weeks vs. 3-6 months). Consequently, we feel strongly that our TSC platform will aid physicians in their decision-making and lead to more effective cancer therapy, while minimizing the toxicities and expense of ineffective drugs. The goals of this proposal are to optimize and validate the assay for traditional chemotherapy and to explore the utility of our platform for testing "targeted" therapies and immunotherapies, all of which are showing great promise in the treatment of human cancers. While our approach applies to all forms of cancers listed in the Fiscal Year 2015 Peer Reviewed Cancer Research Program topic areas, this proposal focuses on CRC as proof-of-principle to demonstrate the versatility of TSC to assess various forms of systemic therapies. We have assembled a team of surgeons, medical oncologist, bioengineer, immunologist, system biologist, and basic pharmacologist across three institutions to bring this technology to the bedside. The key innovations of our work are (1) the development of a quantitative metric to evaluate TSC and to compare results across different samples and patients, (2) the ability to analyze all forms of systemic treatment for any one tumor and to correlate the findings with clinical responses and molecular data, and (3) the adoption of a microfluidic device for high efficiency testing. Upon completion of this proposal, our TSC platform will be ready for clinical application, and we will launch a prospective clinical trial to determine the predictive value of TSC-based testing in patients with liver metastases. Military Service members are exposed to various chemicals, biologics, and environments distinct from civilians, which may contribute to unique genetic and epigenetic alterations. Resulting cancers may exhibit peculiar biology, including response to treatments. As such, conventi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610152
Entities
People
- Venu G Pillarisetty
Organizations
- United States Army
- University of Washington