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School of Medicine
Conquest - The CRF Supports a Decade of Research Funding
Making the Connection Update 2009-2010
The CRF Supports a Decade of Research Funding
Date: May 1, 2010
Cuts Slow Progress, but Investigators Push On
Ten years ago, we could only imagine the difference a decade could make. Research strides pointed to promising gains, and the results met expectations. Maryland, which once led the nation in cancer death rates, dropped to 19th and continues to fall. Adult smoking rates have declined pushing Maryland to fourth best in the nation. Maryland also is leading the U.S. in cancer screening, according to the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance Survey.
CRF programs have not only contributed to the health of Maryland citizens but also to the health of the state economy. For every research dollar spent, $10 more is made through business contracts and other economic development. Kimmel Cancer Center investigators have brought stimulus dollars to the state, winning one of the largest science and medicine grants under the American Recovery and Reinvestment Act. Over a dozen CRF-based research discoveries and technologies have been patented or licensed to outside companies.
Current cuts to the CRF are difficult but understandable given the state’s budget crisis. However, we look forward to the return of full funding, as it was appropriated in 1999 when the CRF was established by the Governor and General Assembly. Maryland was heralded at U. S. Congressional hearings for its Cigarette Restitution Fund, called a model program, and for using its portion of the award from the states’ joint suit against cigarette manufacturers to take on cancer rather than filling budget gaps, as most other states had done.
There is abundant evidence that the CRF has been successful. One of its greatest accomplishments is seen in the young investigators supported over the years who have gone on to be leaders in cancer research and treatment. The work of CRF investigators Victor Velculescu, James Herman, Malcolm Brock, Elizabeth Platz, Shyam Biswal, and others is considered among the best in the field. The CRF provided much-needed support when they were beginning their careers, a critical time when it is often difficult to obtain grants from the Federal government and private donors. As a result, now,
just ten years later, they have published groundbreaking research, including the comprehensive blueprints of cancer genomes, become program leaders in the Kimmel Cancer Center, and used this seed funding to leverage millions more for their research and the research of others.
While we celebrate the success of the partnership between the state and Johns Hopkins, we must be mindful that this progress is fragile. We don’t want to look back a decade from now and find that the great strides we made have evaporated because we did not stay the course.
Visit www.hopkinskimmelcancercenter.org to see Kimmel Cancer Center Director William Nelson, M.D., Ph.D., speak about the ongoing progress of the CRF.
Ten Big Stories of the CRF
Understanding Cancer Genes
In 2001, the CRF gave seed funding to young investigator Victor Velculescu to begin a genome-wide analysis of colon cancer. In 2008, he was part of the world renowned team that mapped the genetic blueprint of not only colon cancer, but breast, brain, and pancreatic cancers as well, opening the door to new targeted therapies for these cancers. Days ago, Veclulescu, CRF researcher Luis Diaz, and team reported new findings that reveal a unique fingerprint for each individual’s cancer. Through a simple blood test, physicians can use the fingerprint of a patient’s cancer for personalized diagnostics, monitoring the effectiveness of therapies, and ferreting out tumor cells invisible with existing technologies.
Epigenetics-The Other Gene Alteration
Epigenetic changes, or alterations that occur to the environment of cells rather than directly to its DNA, are believed to trigger as many as half of all cancers. CRF researchers Stephen Baylin and James Herman were recently recognized by Thomson Scientific’s Science Watch as leaders in the field. In 2002, the duo revealed an epigenetic alteration, called hypermethylation, as a culprit in the origination of lung cancer. In 2008, working with CRF investigator Malcolm Brock, they uncovered a methylation pattern in lung cancers that could predict whether or not the cancer would recur following treatment.
Their findings were revolutionary, uncovering an epigenetic pattern that makes certain cancers, even those as small as a pea, very aggressive. As a result, the CRF funded an epigenetics laboratory, under Brock’s direction, to perform DNA methylation analysis.
In 2004, similar work in leukemia and a pre-leukemia condition known as myelodysplastic syndrome led to clinical trials of a drug that blocks methylation. Results from the trials led to the first FDA approval of a demethylating agent and honors from the National Cancer Institute.
The Science of the Invisible
CRF investigators Vasan Yegnasubramanian and Sarah Wheelan are co-directors of a new next-generation gene sequencing laboratory. The lab is focused around a new device that harnesses into one powerful piece of equipment the most advanced technology in imaging, optics, molecular biology, chemistry, computer science, and engineering to simultaneously sequence millions of gene targets. With six billion bases in the human genome and as many as five separate changes needed for cancer to develop, the technology is essential to ensuring the pace of cancer research. Within the next decade, the researchers expect that people could have their whole genome sequenced for the cost of routine blood work. Wheelan says if you liken the human genome to a sweater, and the sweater is unraveled thread by thread, next-generation sequencing technology put its back together again and spits out important cancer-related data related to each thread.
Watch Sarah Wheelan talk about her research
Watch Vasan Yegnasubramanian talk about his research
Injecting a Cancer Cure
With one injection into each arm, in 2001, CRF investigator Connie Trimble, delivered the first therapeutic vaccine for cervical cancer. The cancer is caused by the human papillomavirus (HPV), so Trimble and team developed a vaccine that prompts immune cells to recognize and attack HPV. Without the virus, cervical cancer cells can’t survive.
With cervical cancer rates in Baltimore City and Maryland’s Eastern Shore three times the national average, Trimble’s vaccine provides real opportunities for saving lives. Phase II trials of the vaccine began in 2009.
Mice that Smoke and the Carcinogen Pump
In a cigarette exposure facility, CRF investigator Shyam Biswal has assembled machines that help mice to smoke so that he can use animal models to study the effect of cigarettes on genes and translate this work to humans. He has zeroed in on a suspicious gene called Nrf2. Biswal revealed that when it works properly, the gene protects humans against carcinogens, directing proteins to absorb pollutants and chemicals, like those in cigarette smoke, and quickly pump them out of the body before they can cause harm. Lung cancer cells, however, corrupt the process hijacking another gene called Keap1 to see anticancer drugs as toxins and prompting Nfr2 to pump them out of cells before they can attack the cancer cells. Biswal is now screening compounds for those that can shut down Nrf2 and improve the effectiveness of lung cancer therapy. Biswal’s Nrf2 pathway also is the focus of other CRF investigators cancer prevention studies. This research has led to discovery licensing, the first step in moving the science to the marketplace.
Broccoli Tea Keeps Cancer at Bay
It turns out that broccoli is high in a cell detoxifying agent called sulphoraphane, turning on enzymes that protect cells from cancer-causing agents. It’s also safe, natural, and cheap, making it a perfect candidate for cancer prevention studies. CRF investigator Kala Visvanathan is harnessing and testing the power of the broccoli-borne compound in clinical cancer prevention trials. With the help of volunteers who have come to Johns Hopkins for breast reduction surgery and prophylactic mastectomies, Visvanathan is studying the effect of a broccoli sprouts tea-like drink on cancer-protective enzymes, comparing the breast tissue of volunteers drinking the broccoli tea with those who do not.
Other broccoli sprouts preparations, oral and topical, also are being studied for their ability to prevent stomach, skin, and lung cancers.
Low Cholesterol Equals Low Grade Prostate Cancer
CRF investigator Elizabeth Platz led a collaborative study that showed men with lower cholesterol slash their risk of developing high grade prostate cancer by up to 60 percent. High-grade prostate cancers tend to grow and spread more rapidly than other forms of the disease. Platz’ new findings confirmed similar results from studies done in 2008 and 2006 that found that men taking cholesterol-lowering drugs, such as statins, were less likely to develop prostate cancer. Platz suspects that cholesterol may affect cancer cells at a level where it influences key signaling pathways controlling cell survival. Cancer cells use these survival pathways to evade the normal cycle of cell life and death. Targeting cholesterol metabolism could be one route to treating and preventing the disease.
Breast Cancer Immunity
Most treatments involve drugs that go after cancer cells directly, but CRF investigator Leisha Emens’ novel therapy goes after the cancer via the immune system. Her breast cancer vaccine changes the way the body sees and reacts to the cancer, causing the immune system to recognize cancer cells and destroy them. She is using the vaccine in combination with standard therapies and novel treatments to improve breast cancer survival. In 2008, Emens’ breast cancer vaccine research and several of her patients were the focus of an award-winning series featured in the Baltimore Sun.
Blocking the Painful Spread of Prostate Cancer
In 2002, Michael Carducci received CRF support to advance his research of the prostate cancer drug atrasentan. It was among the first of the celebrated “targeted” cancer therapies, so-called for its ability to specifically block a protein called endothelin secreted excessively by prostate cancer cells. The protein promotes prostate cancer cell growth and painful spread to the bones. His research showed that the drug stabilizes the spread of prostate cancer for a portion of men with advanced cancer that has stopped responding to standard treatments.
HPV Vaccines for Cervical Cancer Could Also Prevent Oral Cancers
Oral cancers have been steadily rising since 1973. CRF supported the first detailed research of the relationship between the human papillomavirus (HPV) and head and neck cancers. The Kimmel Cancer Center studies proved that HPV is the cause of oral pharyngeal or tonsillar cancers. Further research identified HPV-positive oral cancers a distinct subtype of the disease associated with better treatment outcomes. Currently available HPV vaccines, such as Gardasil, could reduce the rates of HPV-associated oral cancers. The American Society of Clinical Oncology, in 2007, called the findings one of the top cancer advances.
Cigarette Restitution Fund, Johns Hopkins Kimmel Cancer Center