Cold Spring Harbor Laboratory
Cold Spring Harbor, New York
Professor, Cancer Genetics
Understanding the interactions between normal cells and tumor cells to find new strategies to prevent or treat breast cancer.
Tumor cells interact with non-cancer cells and other tissue components that make up the tumor microenvironment, which influences tumor growth and its response to anti-cancer therapies. Dr. Wigler and his team have developed powerful tools to study characteristics of individual cells and how they interact with neighboring cells. They are implementing these tools to assess tumor response to treatment and hope to use this information to develop new drugs for the prevention and treatment of breast cancer.
Dr. Wigler is conducting single-cell genome analysis of cancer cells. He and his team analyzed genome and protein expression status of thousands of single cells from five primary endometrial cancers. They determined the structural tissue components in each sample, which differed among patients but also among samples from the same patient. Dr. Wigler found that the cells of some structural components surrounding tumors have mutated genes—which could play a role in cancer progression—and also that immune cells may travel with cancer as it metastasizes.
In the upcoming year, Dr. Wigler and his team will expand their single-cell studies to observe migratory patterns and distribution of tumor cells and surrounding structural cells within the body. Specifically, the team will assess whether structural cells surrounding primary tumors migrate into the blood stream and spread to metastatic sites along with the cancer cells. Finally, Dr. Wigler will begin preparation for larger studies testing the clinical utility of the tools.
Cold Spring Harbor Laboratory scientist Michael Wigler, PhD, in a prior collaboration with James Hicks, PhD, analyzed 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, the team developed and used powerful technologies 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®.
Dr. Wigler and his team have also developed a sensitive technology called single nucleus sequencing (SNS) that can identify genetic changes in very small samples and provide a method to follow genetic changes as tumors progress and identify specific changes that can predict which tumors are likely to metastasize. His group continues 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.
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