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New Treatment and Research
The Johns Hopkins Kimmel Cancer Center has a long and well-recognized history of innovative research and treatment for colorectal cancer patients. Our Colon Cancer Center is a multidisciplinary program providing comprehensive consultation, screening, diagnostic, surveillance and prevention, and the latest treatment services for patients with cancer of the large bowel and those at risk of developing cancer of the colon and rectum.
Physician-scientists at the Johns Hopkins Kimmel Cancer Center are continuously searching for new and better ways to manage colorectal cancers. In our multidisciplinary program, medical and radiation oncologists, surgeons, and others work together to design individual treatment plans that best meet patient needs. Palliative care is an integrative part of our services.
Our team also is committed to finding new options for patients with metastatic disease, including studies of a live, flesh-eating bacteria called Clostridium Novyi-NT administered through a single intravenous injection. In animal studies, the bacteria selectively targeted colon cancer cells while leaving normal cells unharmed.
Our experts also are using genetic testing when possible to help predict outcomes to therapies. Testing for mutations of the Kras gene, for example, can predict if patients will respond to drugs known as EGFR inhibitors. Another test checks for an enzyme that causes a poor reaction to 5FU, a mainstay drug for colon cancer.
Historically, cancer treatment has focused on drugs that kill all rapidly-reproducing cells – cancerous or not. Dr. Diaz and colon cancer surgeon Michael Choti, M.D., have developed a blood test that detects genetic mutations found in colon cancer. With their test, which measures levels of known cancer-causing mutations in the blood, doctors can tell within 24 hours of surgery if any microscopic cancer was left behind.
Other treatment options for late stage gastrointestinal cancers may include cytoreductive (debulking) surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). In certain cases, the procedures have been shown to be an effective treatment option for certain peritoneal surface malignancy cancers such as selected stage IV colon cancer and other gastrointestinal cancers including appendiceal cancers and pseudomyxoma peritonei.
A new colon cancer vaccine, monoclonal antibody therapy, radio-immunotherapy, imaging-guided and robot-assisted surgery and molecular-targeted therapies are among other new approaches to treating advanced colon cancer.
Scientists at Johns Hopkins found that mistakes in so-called mismatch repair genes, first identified by Johns Hopkins and other scientists two decades ago, may accurately predict who will respond to certain immunotherapy drugs known as PD-1 inhibitors. Such drugs aim to disarm systems developed by cancer cells to evade detection and destruction by immune system cells.
In addition, our scientists are studying the link between dense mats of interacting bacteria, called biofilms, present in colon cancers and pre-cancerous polyps. These bacterial bunches, they say, may represent an increased risk for colon cancer and could form the basis of new diagnostic tests. The scientists believe that these biofilms aid digestion, metabolism and immunity in normal circumstances, but may promote inflammation in the colon, which is often linked to cancer.
Colon Cancer Vaccine Research
The Susan Cohan Colon Cancer Foundation presented Lei Zheng, M.D., Ph.D., with $250,000 to fund a colon cancer vaccine research program. The fund were raised thru the annual Susie's Cause 5K run/walk event.
The research will test a immune based vaccine and demethylating agents as new ways to treat colon cancer.
Zheng and his colleagues recently completed a phase 1 clinical trial of a colon cancer vaccine. Now, with the new funding support from the Susan Cohan Colon Cancer Foundation a new clinical trial will be developed to test the combinational therapy of the vaccine and demethylating agents in metastatic colorectal cancer patients who have completed chemotherapy.
For more than 25 years at the Johns Hopkins Kimmel Cancer Center, internationally renowned cancer researcher Bert Vogelstein and colleagues have slowly been unraveling the genetic mysteries of colorectal cancers. His discoveries have led laboratories across the country to develop genetic tests, screening diagnostics and targeted therapies for colon and other cancers.
Dr. Vogelstein and his laboratory personnel have made many significant findings in cancer genetics. In 1989, they identified in colon cancers mutations in a gene called p53, starting a media frenzy as investigators around the country found similar mutations in breast, lung and other cancers. These mutations occurred late in cancer development, prompting Dr. Vogelstein to hypothesize that colon cancer results from a series of genetic alterations evolving over decades.
To study the whole series of mutations and the order in which they occur, he decided to look at inherited colon cancer syndromes. Though these colon cancers were more rare, he felt the same genetic underpinnings affecting families could shed light on all colon cancers. Vogelstein, lab co-director Kenneth Kinzler, pathologist Stanley Hamilton and others identified a mutation of the APC gene in Familial Adenomatous Polyposis (FAP), a rare inherited syndrome marked by hundreds of benign colon polyps. Additional studies found the same mutation jump starts the cancer process in the nearly 140,000 people diagnosed with colon cancer each year.
Other researchers in the lab discovered the genetic and biochemical basis of hereditary non-polyposis colon cancer (HNPCC), accounting for more than 50 percent of inherited colon cancer syndromes. In 1998 the team reported a genetic alteration affecting as many as 400,000 people nationwide---6 percent of Ashkenazi, or European-descendant Jews. The finding catapulted genetic testing for cancer into mainstream medicine.
Based on the APC finding, the lab set out to look for mutations in colon cells shed and passed in stool, hoping that if they found APC mutations they could potentially prevent cancer from occurring. They went on to develop a safe and reliable stool test that can detect the earliest, curable stages of colon cancer. Early studies of the test, which uses a newly developed technology to detect and highlight a key genetic marker of the disease, were reported in a 2002 issue of The New England Journal of Medicine.
Building on that work, a series of studies by researchers here and at other institutions around the world published in 2009 identified four potential biomarkers for colorectal cancer that appear in affected patients’ stool, paving the way for new, noninvasive methods of screening for colorectal cancers. The studies indicate that methylation – a chemical process that alters a gene’s expression – in the genes TFPI2, GATA4, GATA5, and NDRG4 occurs early and frequently in colorectal cancers. The altered genes were identified in stool samples from colorectal cancer patients but were rarely seen in samples from people who did not have cancer, indicating that stool tests to check for these changes could be effective in early identification of colorectal cancers. Ongoing research efforts will examine if searching for more than one marker at a time could identify additional cancer patients; look for additional genes that may serve as potential biomarkers of disease; and see if testing methods can be made more accurate.
Read an article about Dr. Vogelstein’s work from the cancer center’s Promise and Progress newsletter.