Colorectal Cancer

 Background

In the United States, an estimated 108,000 new cases of colon cancer and 41,000 new cases of rectal cancer were diagnosed in 2008. In fact, colorectal cancer is the third most common cancer in both males and females and accounts for about 10% of cancer deaths each year.

The death rate from colorectal cancer has decreased over the past two decades in the United States, thanks to the progress made in early diagnosis and in the treatment of this disease. Still, 36% of patients with colorectal cancer will not survive longer than five years after initial diagnosis.

New and more effective therapies will produce a major improvement in survival rates among colorectal cancer patients. NFCR funds a number of leading scientists who are conducting cutting-edge research grounded in the newest technologies seeking to discover new biomarkers associated with colorectal cancer. These biomarkers are essential to the development of new tools for diagnosis and better treatment options for patients with colorectal cancer.

Research

Below are brief descriptions of three outstanding research projects NFCR is currently supporting in our quest to deliver new hope for colorectal cancer patients.

Shutting down cancer through anti-angiogenesis
NFCR Fellow Harold F. Dvorak, M.D., Beth Israel Deaconess Medical Center

Dr. Dvorak discovered vascular endothelial cell growth factor (VEGF), which encourages and supports new blood vessel growth, otherwise known as “angiogenesis.” His groundbreaking discoveries changed the very face of cancer research, since VEGF is also required for the formation of new blood vessels which nourish and support malignant tumors. Dr. Dvorak’s breakthrough had a major infl uence on the research efforts of many other vascular scientists, and this has now led to the development of anti-angiogenic drugs that target VEGF such
as AvastinTM.

Today, Avastin, in combination with chemotherapy, is recommended for first-line treatment of patients with metastatic (spreading) colorectal cancer and lung cancer, as well as for treatment of a subgroup of patients with metastatic breast cancer. As is common with many anti-cancer drugs, Avastin is not a “silver bullet” treatment that works for every patient with colorectal cancer. Dr. Dvorak’s research suggests that there are many types of tumor blood vessels, each with different structural and molecular properties. Some of these blood vessels may not be susceptible to Avastin and consequently, some patients’ cancer fails to respond to the specific molecular mechanism which makes Avastin’s anti-angiogenic effect possible.

With NFCR’S support, Dr. Dvorak and his team are searching for new markers of each type of tumor vessel. Their hope is that by identifying more specifi c biomarkers, they can provide researchers with unique targets around which new and more effective anti-angiogenic drugs can be developed for colorectal cancer patients.

Identifying surrogate markers for AvastinTM
NFCR Project DirectorRakesh Jain, Ph.D., Massachusetts General Hospital

Avastin inhibits tumor blood vessel formation and is used for treating patients with metastatic colorectal cancer. However, not all patients respond to Avastin. In order for oncologists to achieve optimal results for their patients, they must have the ability to adjust treatment options without wasting their patients’ precious time. Dr. Jain’s team is trying to develop a method for determining, as early as possible, whether or not a patient is likely to respond to Avastin treatment.

He is identifying surrogate markers which would allow doctors to monitor how effective Avastin is in individual patients at an early stage in their treatment. He and his colleagues, Drs. Jeffery Clark and Christopher Willet, who are also leaders in clinical oncology and new therapy development for colorectal cancer, are treating colorectal cancer patients with Avastin combined with chemoradiation therapy in a clinical trial. Using a multiplex assay, the research team has measured the levels of multiple protein biomarkers in patients’ blood. Results show that patients who respond well to Avastin also have increased blood levels of VEGF and PIGF (placental growth factor) early in their treatment. Moreover, patients with low blood levels of VEGFR1 (VEGF Receptor 1) and PIGF prior to Avastin treatment experienced more side effects during treatment.

Dr. Jain and his colleagues may have found the most promising quantitative indicators to measure early response to anti-angiogenic agents and predict their side effects. Dr. Jain’s team is identifying other molecular markers in colorectal cancer patients that may also prove useful in evaluating the potential impact of anti-angiogenic therapies. These discoveries are essential steps in developing tools that will enable physicians to customize anti-angiogenic therapy for their patients, achieving optimal treatment efficacy in individual colorectal cancer patients.

Development of a new biomarker and therapeutic target
NFCR Project Director Wei Zhang, Ph.D., M.D. Anderson Cancer Center

Although studies of genes and proteins over the past 10 years have produced potential candidate markers, more in-depth investigation is required to determine whether these marker genes are key oncogenes (cancer promoting genes) that initiate the abnormal pathways that give rise to colorectal cancer.

Through a series of analyses using tumor samples from colorectal cancer patients, Dr. Zhang discovered that NGAL, a protein normally expressed in white blood cells, is produced in abnormally high amounts in colorectal tumors. This important finding suggests that NGAL may be a new colorectal cancer biomarker and therapeutic target, but first, Dr. Zhang must determine whether excessive production of NGAL is the key driving force in colorectal cancer development. Using laboratory cancer cell line cultures, Dr. Zhang has demonstrated that NGAL confers cancer specific properties to cells: NGAL makes non-invasive cells more invasive. His team is currently identifying the molecular players associated with NGAL in colon cancer cells – a crucial step in the understanding of its role in the development of colorectal cancer. Dr. Zhang’s research on NGAL will soon determine if it may become a new biomarker for early diagnosis, and a therapeutic target for treatment of colorectal cancer.

How You Can Help

These research projects hold great promise for yielding more effective therapies for colorectal cancer. With more funding, however, they could ramp up their efforts and accelerate progress to save more lives! When you donate to NFCR, your dollars help our scientists accomplish many important research goals aimed at developing better cancer treatment and prevention strategies. Click here to learn more

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