Professor, Cancer Genetics
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Tumors are composed of a complex mixture of cells with different genomic makeups that influence response to treatment and tumor behavior. Technology developed by Dr. Wigler in collaboration with BCRF grantee James Hicks makes it possible to study the complexity of breast cancer at the single cell level and to begin developing new diagnostic tools that will aid in therapeutic management of the disease. Since developing the first single cell genomic methods in 2011, Drs. Wigler and Hicks have applied the continued support of BCRF to the dual goals of improving the technology and applying it to the challenge of providing physicians with new diagnostic tools that will take breast cancer therapy to a new level of precision and effectiveness. In the coming year they will focus on profiling the genome of rare cells and circulating DNA in samples of blood. Using a novel technology called RepSeq they will be able to reduce the cost of single cell genomics, making the technology accessible for large-scale clinical trials, while advancing another sequencing-based technology for the early detection of recurrent breast cancer through a blood test. These projects have enormous potential, not only for detecting cancer recurrence at the earliest stages when it can be treated, but also for measuring residual disease in adjacent normal tissues, and detecting and measuring point mutations. They will help to direct oncologists toward new generations of targeted therapies. In addition the research team’s studies on the tumor microenvironment will advance our understanding of how cells become metastatic, and the role of the immune system in that process and in therapeutic response.
Cold Spring Harbor Laboratory scientist Michael Wigler, PhD, in collaboration with James Hicks, PhD, is analyzing the genomes of women with breast cancer in research aimed at eliminating "trial-and-error" approaches to therapy. This work is leading to diagnostic tests capable of distinguishing cancers likely to spread and should receive aggressive treatment from those that are benign and can be left untreated. In this effort, Drs. Wigler and Hicks are using powerful technologies that they developed to analyze genomic and epigenetic changes in thousands of breast cancers and have identified three distinct categories of breast cancer DNA profiles associated with different outcomes for patients. Their research has provided important information about which patients are most likely to benefit from treatment with specific drugs, such as taxol and Herceptin®. Drs. Wigler and Hicks have also developed a sensitive technology called single nucleus sequencing (SNS) that can identify genetic changes in very small samples, which can be used to follow genetic changes as tumors progress and to identify specific changes that can predict which tumors are likely to metastasize. The group is continuing to make technological improvements to make it affordable and feasible for SNS to be used as a monitoring tool for early detection of cancer cells in the blood, and to direct therapy based on the genetic makeup of those circulating cancer cells.