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Taming the tsunami
SAN FRANCISCO & SAN DIEGO--Researchers from the University of California, San Diego (UCSD) School of Medicine and University of California, San Francisco (UCSF), with support from a diverse team of collaborators, have launched an ambitious new project that may last 20 years and could make personalized medicine a practical reality.
The Cancer Cell Map Initiative (CCMI) has been created to determine how all of the components of a cancer cell interact. It was motivated by the “tsunami of genomic information available” in recent years, but the inability to make sense of it, according to said Dr. Nevan Krogan, director of the UCSF division of life-sciences research institute and accelerator QB3, an investigator at Gladstone Institutes and co-director of CCMI with Dr. Trey Ideker, chief of medical genetics in UCSD’s Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics.
“We’re going to draw the complete wiring diagram of a cancer cell,” Krogan explains. “We’re going to use network biology to make sense of genomic data, make physical maps of proteins and genes and introduce mutations to see how functions are perturbed.”
While progress in genome sequencing enables researchers to decipher hundreds of mutations found in a patient’s tumor, scientists rarely understand how these mutations cause cancer or indicate treatment plans. Mutations in each patient are usually different, but they can lead to the same type of cancer. Inasmuch as these mutations are unique to individuals, they attack the same cancer pathways or genetic circuits. The complete wiring diagram of the cell will establish all of the connections between normal and mutated genes and proteins.
“We have the genomic information already. The bottleneck is how to interpret the cancer genomes,” says Ideker. A comprehensive map of cancer cells would help—and accelerate the development of personalized therapy, the central aim of what has come to be called precision medicine. This process, according to Ideker, “will enable applications to start with the genome, identify the genes, determine their interactions and use the information for personalized treatment.”
Krogan adds, “The key to understanding genomic information is being able to place it into biological context. Mutations in tumor DNA that at first appear to be unrelated may in fact be clustered in specific pathways or multiprotein machines in the cell. The information, in context, will point to areas that we can target with specific therapies.”
The CCMI is a multimillion dollar collaboration between the UC San Diego Moores Cancer Center and the UCSF Helen Diller Family Comprehensive Cancer Center; funded by QB3 at UCSF, UC San Diego Health Sciences and support from Fred Luddy, founder of ServiceNow, a provider of enterprise service management software. Thermo Fisher Scientific is providing mass spectrometers to characterize protein-protein interactions.
The project combines UCSD’s expertise in extracting knowledge from big biomedical data sets with advances developed at UCSF for experimentally interrogating the structure and function of cells. Both schools have two comprehensive cancer centers with samples that constitute a library of mutations associated with the disease. Actual patients with cancer and the stories contained within their DNA will drive the project, according to the researchers.
UCSD’s primary mission will be to provide tools for network generation and integrate them into the project to visualize the effects of mutations on cells. UCSF will contribute its ability to generate pluripotent stem cells and its expertise in genetic engineering.
Additionally, the CCMI will provide key infrastructure for the recently announced alliance between UC San Diego Health Sciences and San Diego-based Human Longevity Inc., which plans to generate thousands of tumor genomes from UC San Diego cancer patients. It will also leverage resources and information from the National Cancer Institute (NCI), including large databases of cancer genomes and pathways that are being developed in collaboration with the San Diego Supercomputer Center and UC Santa Cruz.
David Haussler, director of QB3 at UC Santa Cruz and creator of the NCI Cancer Genomics Browser, said, “This is an exciting opportunity to utilize the unique NCI repository of 1.5 petabytes of cancer genomics data, combined with proteomic and functional data, to dive deeper into the molecular processes of cancer.”
For the near term, CCMI will compare healthy cells to tumor cells to see how treatments work on various mutations. Researchers will simplify the procedure to find three or four pathways to tailor a particular treatment, not treat patients with a drug that has an effect on everything. Initially, CCMI will focus on breast and HPV cancer, including head and neck and cervical, and then address subcategories. Eventually, the researchers hope to use genomics to look at other diseases.
“Eventually, patients will be able to go to their doctors and get genome sequences that will interpret the diagnosis of diseases and suggest a path to the cure,” Krogan concluded. “The specific goal is personalized medicine.”