A BCRF investigator since 1998, Dr. Michael Wigler along with BCRF colleague, Dr. James Hicks pioneered single cell analysis, the process of isolating single tumor cells to study the underlying tumor biology. This technology paved the way for the development of liquid biopsy, a non-invasive way to potentially measure tumor response to treatment or risk of recurrence from a sample of patient blood.
Using sophisticated cell sorting and DNA sequencing technologies developed in his lab, Dr. Wigler’s current BCRF research is seeking to characterize the interaction between normal (host) cells and tumor cells that will inform new strategies to prevent or treat breast cancer.
There are three primary areas of research supported by BCRF that laid the groundwork for much of Dr. Wigler’s work, particularly in single cell analysis. Below he describes each in greater detail.
1. Building the infrastructure
At the beginning of our BCRF funding, we were just starting to utilize genomics to look at the differences between cancer cells and normal cells. That early work, facilitated by a gift from the Lillian Goldman Charitable Trust to BCRF, supported the development of the critical infrastructure for our work in cancer genomic analysis.
One of our earliest observations was the discovery that it was possible to predict the malignancy of a breast cancer by its genomic profile. We discovered, however, that our predictions were not always accurate. This is when we realized that different pieces of tumor contain different information. Depending on what part was analyzed, the information may not have been predictive of tumor behavior. This led us to develop methods to isolate and analyze the genes of single cells, all of which was done with BCRF support.
2. Moving from the tumor to single cells in blood
When we began to look at single cells in tumors, we discovered the tumors were made up of a mixture of tumor cells with different genomic profiles, some being more malignant than others. This explained why our earlier attempts led to inconsistent predictions of tumor outcomes. We then began our work to look for cancer cells in blood to gain a more accurate picture of the tumor.
One of the important clinical applications of this technology is to be able to monitor patients during and after treatment. To tackle this challenge, we developed a method we call sensitive detection, which works by detecting circulating tumor cells based on their unique molecular tags.
The technology makes it possible to detect one tumor cell in one million cells. This means we are very close to being able to measure minimal residual disease – disease remaining after treatment that would be undetectable by imaging– by measuring cells in the blood. This advancement was only possible through BCRF seed funding that led to large scale funding from the Simons Foundation.
3. Creating a pathway for others to do the same thing.
I believe we have the technology now to be able to use liquid biopsy for early detection of cancer. In a recent article published in the journal Trends in Molecular Medicine, we describe a method that uses a combination of molecular techniques to detect circulating tumor cells (CTC), even when they are present in as few as one cell per milliliter of blood. Once CTCs are identified, a more stringent molecular analysis can be used to confirm the risk of malignancy and possibly identify the tissue site of the cancer, thus guiding possible diagnosis and treatment.
We are very close to some spectacular technology advances that will continue to move the field forward, none of which we could have achieved without BCRF support.
You can read more about Dr. Wigler’s BCRF research here.
Dr. Wigler’s research is generously underwritten by donations through Play for P.I.N.K.
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