Dr. Pia Morelli with Fight Colorectal Cancer Board Chair Nancy Roach

Fight Colorectal Cancer and its generous Lisa Fund donors struck a blow against late stage colorectal cancer Tuesday, April 9th at the 2013 annual meeting of the American Association for Cancer Research (AACR) in Washington D.C.

Top cancer researchers from around the nation applauded as we, along with the AACR, awarded a $50,000 research grant to Pia Morelli, M.D., Ph.D., a post-doctoral Fellow at the University of Texas MD Anderson Cancer Center in Houston.

With this grant, Dr. Morelli will use highly specific DNA tests on blood samples to identify those patients most likely to respond to drugs that target the Epidermal Growth Factor Receptor (EGFR), and also to detect even more specific KRAS and EGFR mutations that develop over time, which perhaps cause patients to eventually become resistant to anti-EGFR drugs such as Erbitux (cetuximab) and Vectibix (panitumumab).

Currently, tumors of late-stage colorectal cancer patients are tested to detect a KRAS genetic mutation. If they have the mutation, they do not receive Erbitux or Vectibix. However, even those who have wild-type (non-mutated) KRAS and initially respond to anti-EGFR treatments can develop resistance and no longer benefit from these powerful drugs.

Researchers now understand that cancer is usually a “cascade” of events–often involving more than one genetic mutation and/or abnormal cell functions.–and that over time, patients may develop new mutations, even in different sections of one tumor. However, tumors are always leaking DNA into the blood stream. In her research, Dr. Morelli will analyze blood samples of colorectal cancer patients using a highly specialized new technique of DNA analysis that can detect these less frequent mutations that can occur in both the KRAS gene  and in EGFR cell-wall mutations over time, and that might cause chemotheraphy resistance. The ultimate hope would be to eventually use blood DNA analysis instead of repeated tumor biopsies to monitor cancer cell changes during disease progression and treatment.

Working at MD Anderson, she will be able to test large numbers of blood samples to see if the highly sensitive DNA analysis can better predict both initial response and/or developing resistance to the anti-EGFR targeted drugs.

Dr. Morelli graduated summa cum laude in medicine and started her medical oncology fellowship at the Second University at Naples School of Medicine, where she had the rare chance to do “translational research”—doing both patient care and  laboratory research on the EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor receptor) that stimulate tumor growth. Recruited to the University of Colorado Cancer Center, she completed her medical oncology fellowship and a Ph.D. with world-renowned Dr. Gail Eckhardt, continuing her laboratory research into targeted drugs plus running Phase I clinical trials. She then worked two years at the Spanish National Cancer Research Center, and in 2012 came to the MD Anderson Cancer Center.

According to her supervising mentor, Scott Kopetz, M.D., Ph.D, at the MD Anderson Cancer Center, Dr. Morelli has “a unique insight into questions of particular clinical relevance….She is able to maximize the information derived from patient-based studies [combined with]…her unique molecular biology background.”

Her research, he said, is “anticipated to have profound impact on clinical outcomes.”

An AACR expert committee selected Dr. Morelli as winner of the 2013 Fight Colorectal Cancer-AACR Fellowship, given annually in memory of the late Lisa Dubow.

One of just a few AACR fellowships–and the only one focused on late-stage colorectal cancer–it is funded 100% by donations to the Lisa Fund at Fight Colorectal Cancer.

Lisa Dubow, one of the founding members of Fight Colorectal Cancer, directly credited researchers for giving her extra years of survival with stage IV colorectal cancer. Before her death, she launched what became known as the Lisa Fund to support young scientists who chose advanced (metastatic) colorectal cancer as their research focus.

Andrea Bertotti, MD, PhD

Andrea Bertotti, M.D., Ph.D. 
Istituto per la Ricerca e la Cura del Cancro, Candiolo, Italy 

Improving targeted therapy in colorectal cancer through xenopatients

Grant amount: $100,000 over 2 years

Dr. Bertotti has created a unique collection of “xenopatients”–mice which are implanted and living with more than 300 different human colorectal cancer tumors. Each tumor has been meticulously analyzed for gene expression, exome, and cell pathways. With this grant, he will be able to test (in mice rather than in patients) how specific human tumors with defined genetics respond to specific drugs and combinations. Bertotti’s work will also speed the search for biomarkers—tests that could predict which drug will work for an individual’s specific metastatic colorectal cancer.

Dr. Bertotti’s research marks a milestone for Fight Colorectal Cancer: It is our first-ever two-year $100,000 grant to a scientist whose work fights advanced stage colorectal cancer.

Dr. Bertotti has already made a mark in colorectal cancer research. “Andrea has stood out as one of the most brilliant young scientists of our institution,” said Dr. Paolo Comoglio, Scientific Director of the IRCC. He led “a huge institutional effort” to create the library of genetically analyzed human tumors transplanted into mice. With those human tumor samples, the laboratory will focus on the 40 percent of human metastatic cancer samples in which the tumor is held stable—but does not shrink—when treated with Erbitux (cetuximab).

Using the mouse models, the lab will be able to safely test a combination treatment, adding lapatinib (another drug which works similarly but in a different pathway than Erbitux). The scientists will analyze the cells, looking for biomarkers that predict response to the treatments, as well as other pathways for which new drugs could be developed. If the drugs substantially shrink a subset of tumors, the research could potentially move into clinical trials.

“His work will be ground-breaking and exactly in line with the reason Lisa Dubow created this fund—to support a promising researcher working to advance the treatment of metastatic colorectal cancer,” said Carlea Bauman, president of Fight Colorectal Cancer.

Make an investment in colorectal cancer research. Donate to the Lisa Fund today.

by Mary Miller

Fight Colorectal Cancer is thrilled to announce during this holiday season that thanks to the generous donations made to the Lisa Fund, it will be awarding its first-ever two-year $100,000 grant to a scientist whose work fights advanced stage colorectal cancer.

Andrea Bertotti, MD, PhD, of the Institute for Cancer Research and Treatment (IRCC) in Candiolo, Italy, has learned that his lab will receive this major grant. “His work will be ground-breaking and exactly in line with the reason Lisa Dubow created this fund—to support a promising researcher working to advance the treatment of metastatic colorectal cancer,” said Carlea Bauman, president of Fight Colorectal Cancer. Fully 100 percent of donations go directly to support young scientists. Each year’s winner is selected by an expert panel of researchers, through a review process administered by the American Association for Cancer Research. Read the rest of this entry »

Pausing today to give thanks for this amazing Fight Colorectal Cancer community, we’d like to especially salute the doctors, nurses, family and friends who work every single day to support people living with colorectal cancer, and to the researchers who devote endless days and nights fighting this disease.

Just before the holiday, we got a final progress report from Dr. Jon Chung, who received the 2011 Lisa Fund grant.  Every single dollar that supported his work came from this community of people who donated to the Lisa Fund, so you should know what your generous donations brought:

“I am extremely grateful for the award of this grant. It has been hugely beneficial in my career. Since the end of the grant funding period, I have been promoted to faculty at Johns Hopkins…As a result of this grant, the laboratory has developed a firm interest in developing [new] inhibitors for Hedgehog signaling…in colorectal cancer—an area of research that had not been previously a focus of the laboratory. I believe that the focus cancer signaling pathways will be a feature of my current and future career as a cancer researcher.”    

Dr. Chung is researching one of the signaling ‘pathways’ that cause colorectal cancer to change from localized to metastatic disease. During his Lisa-funded year, he and his coworkers identified a new gene involved with activating Hedgehog, which eventually could lead to a new biomarker test.

So thank you: Not only did your contributions build a concrete step forward in the fight against metastatic cancer, but you made a life-changing impact on a promising young scientist—and a whole laboratory.

At our Thanksgiving tables today, there are a few beloved faces missing—I think of Lisa Dubow, who started the Lisa Fund as thanks for researchers who gave her an extra 9 years of life. And I think of Kate Murphy, who started this blog to bring Research news to you, and who also used her years living with cancer to make a huge impact on countless lives.

In the great circle of life, their legacy lives into the future, thanks to people like Dr. Chung and you in this community.

 Read more: about Dr. Chung’s work,  and Lisa Dubow.

Jon Chung PhD

Dr. Jon Chung
Johns Hopkins University School of Medicine

HEDGEHOG PATHWAY TARGETED THERAPEUTICS FOR METASTATIC COLORECTAL CANCER

Grant amount: $45,000

Dr. Jon Chung is studying alternatives to the traditional Hedgehog signaling pathway in colon cancer cells.  He is exploring crosstalk within the cell between the Hedgehog and Wnt pathways and screening for drugs that block both pathways at the same time, potentially stopping cancer development.

He is also looking at how Hedgehog interacts with DNA damage pathways — research that could lead to treatment that would destroy metastatic cancer cells.

From Dr. Chung’s research proposal:

The Hedgehog signaling pathway has recently emerged as another key player in colorectal carcinogenesis and this pathway is progressively activated during metastasis.  The switch to Hedgehog pathway activation that occurs as tumors metastasize presents an opportunity for developing therapies for metastatic colorectal cancer.  My project will focus on targeting the Hedgehog pathway.

Hedgehog is a gene that is critical to the development of the human embryo.  Signals controlled by the gene direct cells to express themselves as different parts of the body with different functions.  When Hedgehog expression isn’t normal, its changes can lead to cancer, particularly cancer that spreads to distant sites (metastasizes).

Recently, drugs to treat colorectal cancer that directly inhibit the Hedgehog pathway have been disappointing. Dr. Chung is taking a new and different look at Hedgehog signals, particularly when they interact with other important colorectal cancer pathways.

Dr. Chung is a postdoctoral fellow at the Johns Hopkins University School of Medicine in the Department of Radiation Oncology & Molecular Radiation Sciences.

He attended the University of Cambridge where he received his BA and MSci degrees in Natural Sciences (Biochemistry) in 2002. In 2006, he completed his PhD at the University of Manchester. After finishing his PhD, he started postdoctoral research in the laboratory of Dr. Fred Bunz at Johns Hopkins where he has been investigating DNA damage checkpoint and p53 responses in colorectal cancer cells.

Dr. Chung has published research in:

• PLoS Genetics, Cdk2 Is Required for p53-Independent G2/M Checkpoint Control,February 6, 2010, e1000863.
• Cell Cycle: Checkpoint bypass and cell viability, Volume 9, Issue 11, February 26, 2010.

Please help support innovative research like Jon Chung’s with a gift to the Lisa Fund.