Dr. Jeffrey Chou

Jeffrey Chou, M.D.,Ph.D., is the recipient of the 2009 AACR-Colorectal Cancer Coalition Fellows Grant in memory of Lisa Dubow.

Dr. Chou, a researcher at the Fred Hutchinson Cancer Center at the University of Washington in Seattle, will study how to make colorectal cancer stem cells more vulnerable to the body’s immune system.

The award will be made at the AACR’s 100th Annual Meeting in Denver.  Funds for the grant were raised by C3 through the Lisa Fund. Donations to the fund are targeted for research to develop treatments for patients with late-stage colorectal cancer.

Dr. Chou will be working with both cell cultures and mice to see if the drug decitabine will make colorectal cancer stem cells respond to immunotherapy.  He has identified a protein that is specific to cancer which can be recognized as foreign by the immune system.  Once recognized, the cancer/testis antigen NY-ESO-1 elicits a strong immune response that can kill cancer stem cells.

During his research, Dr. Chou will be trying to find out

• If decitabine increases NY-ESO-1 in colorectal cancer stem cells,
• If treating those cells with decitabine and immunotherapy and transplanting them in mice prevents their growing into cancer, and
• If decitabine and immunotherapy can destroy existing colorectal cancer tumors in mice or slow their growth.

Dr. Chou says,

Results from my proposed studies may potentially provide pre-clinical data supporting a novel therapy using a combination of decitabine and immunotherapy for metastatic CRC. I am honored by and grateful for the generous support provided by AACR, C3: Colorectal Cancer Coalition, and the Lisa Fund, and I would like to thank my mentor Dr. Edus Warren, who has been invaluable in fostering my development as a cancer researcher.

AACR Fellows Grants are made to young researchers to encourage their scientific work in cancer:

The Fellows Grants support innovative research by a meritorious young investigator by presenting the Fellow with research funds to pursue an independent line of investigation within the context of his/her current Fellowship placement. By allowing a Fellow to acquire the equipment and supplies needed to pursue a new direction in his/her research program, the Fellows Grant assists the Fellow in developing preliminary data to support a future project or investigating a new technique that otherwise would not be possible in the absence of this funding.

Lisa Dubow

Lisa Dubow, who died in 2007, credited her nine years of survival with advanced colorectal cancer to cutting edge research and participation in clinical trials.

Before her death she worked with C3 to create the Lisa Fund to focus on better treatment for metastatic disease.  Lisa asked that we not forget about her and other patients battling the hard-to-treat late-stage cancer that had already gotten worse on standard treatments.

Your donation to the Lisa Fund is an investment in colorectal cancer research. Help us assist other researchers looking for better treatments and a cure for colorectal cancer by making a donation to the Lisa Fund today.

Jeffrey Chou, M.D., Ph.D.
Fred Hutchinson Cancer Center at the University of Washington

Epigenetic modulation of colorectal cancer stem cells for immunotherapy

As the recipient of the 2009 Lisa Dubow Research Fellows Grant, Jeffrey Chou, M.D., Ph.D. will study ways to make colorectal cancer stem cells more vulnerable to the body’s own immune system.

He will be working with both cell cultures and specially-bred mice to see if the drug decitabine can increase levels of a specific protein that induces a strong immune response.  If so, a combination of decitabine and a vaccine against that protein might be an effective treatment for advanced colorectal cancer.

In his proposal, Dr. Chou writes,

“Despite advances in surgery, radiation, and chemotherapy, the majority of patients with advanced or metastatic disease ultimately die from their cancer. Treatment failures in colorectal cancer may be due to incomplete elimination of the colorectal cancer stem cell which can initiate and sustain tumor growth. Thus, an urgent need exists for the development of better systemic therapies which target the colorectal cancer stem cell.”

Colorectal tumors are composed of different cell types. A small number of tumor cells have the ability to move from where they first developed to new sites in the body to establish new tumors. Cells with this property are called cancer initiating stem cells. These cells are particularly resistant to chemotherapy. Even if 99 percent of a tumor is killed by chemo or other therapy, but cancer stem cells remain, the tumor will grow back and continue to spread.

Find new ways of targeting and destroying colorectal cancer stem cells may lead to new and more effective treatment for colorectal cancer.

One way to destroy cancer stem cells is to harness the body’s own immune system to recognize them as a threat and eliminate them.  Ordinarily, the immune system accepts the proteins in cancer as a normal part of the body and basically ignores them.

However special proteins known as cancer/testis antigens (CTAs) stimulate an immune response in many cancers.  CTAs are only found in cells in the testicles, where they are invisible to the immune system, and in some cancers.  Because they are not found in normal tissue outside of testes, an immune system attack on cells with CTA can target cancer and leave healthy cells alone, ideal for cancer treatment.

Unfortunately, colorectal cancer cells have very low levels of CTAs so treatments for advanced colorectal cancer that evoke immune response (immunotherapy) haven’t been very effective. However, preliminary data show that the drug decitabine increases CTA levels in many types of cancers allowing  immune system cells to recognize and kill them.

One cancer/testis antigen (NY-ESO-1) induces strong immune responses in cancer cells.  Immune cells called cytotoxic T lymphocytes (CTLs) that can specifically recognize and kill cells producing NY-ESO-1 have been discovered.  When colorectal cancer cells are treated with decitabine in the laboratory NY-ESO-1-specific CTLs kill the cancer cells but not normal or untreated cells.

Dr. Chou is planning to build on this knowledge in his research, asking three questions:

• Will treating colorectal cancer stem cell cultures with decitabine increase the levels of NY-ESO-1 in those cells?
• If colorectal cancer cells are treated with decitabine and immunotherapy (cytotoxic T lymphocytes) and transplanted into mice, will the mice develop cancer?
• Can treating mice who already have cancerous tumors with decitabine slow tumor growth or destroy those tumors completely?

If successful, Dr. Chou’s basic research with colorectal cancer cells and mice may lead to effective vaccine therapies for colorectal cancer, killing the stem cells that keep it from being completely eliminated by conventional treatments.

The choice of Dr. Chou’s proposal for the 2009 award was made in collaboration with the American Association for Cancer Research (AACR) as part of its Fellows Grants Program for talented young investigators.

Lisa Dubow dreamed of a day when even the most dangerous and deadly colorectal cancer could be cured. You can help Fight Colorectal Cancer make those dreams come true by supporting the work of imaginative young cancer researchers by investing in the Lisa Fund.