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Knowledge is power
Pondering the immensity of time, a century is but a few grains of sand in the hourglass of science through the ages. When you consider the timeline of cancer research, the last 100 years overshadow developments in all of the preceding years combined, and many advances started on laboratory tables in halls of academic institutions.
With advances made through drug research and discovery, physicians have moved from being able to do very little to help patients with cancer to achieving survival rates that were never thought to be attainable.
Cancer research began to explode in the late 19th and early 20th centuries, and the use of X-rays and Radium was in its infancy. In the United States, institutes for research were being established, including Roswell Park, the Rockefeller Institute and the Institute of Cancer Research at Columbia University. Additionally, private endowments to fund research were beginning to spring up to give a funding boost to efforts that showed promise.
In the last couple of decades, researchers have learned an enormous amount of information about the molecular mechanism of how normal cells are transformed into cancer cells. Many big pharmaceutical companies have jumped on these novel findings and produced kinase inhibitors to target oncogene-activating signals or antibodies directed toward receptors on the surface of cancer cells. Also, other inhibitors, such as PARP inhibitors, have been developed.
Today, academic institutions remain on the cutting edge of research and development of novel treatments for cancer. In this, the fourth installment of our Trends in Cancer Research series, we will examine the role of academia in cancer research.
Being at the forefront of academic cancer research can have its benefits, as witnessed by the recent announcement that Sanford-Burnham Medical Research Institute has been recognized as "outstanding" by the National Cancer Institute (NCI) and has had its NCI-designation renewed for five years. The institute has been an NCI-designated basic research cancer center continuously since 1981.
Along with the most recent designation comes a five-year core grant renewal, which provides more than $21 million to support advanced cancer research at Sanford-Burnham, a 21 percent increase over the previous grant.
"NCI Cancer Center designation is a national benchmark, and our renewal with an 'outstanding' rating confirms the exceptional quality of cancer research at Sanford-Burnham," says Sanford- Burnham President Dr. Kristiina Vuori. "The significant budget increase we received is a tremendous honor and a reflection of the hard work and dedication by faculty and staff throughout the institute."
The institute has set the bar high for itself, and its teams continue to make great strides in the area of cancer research. In recent months, Sanford-Burnham researchers have made several exciting breakthroughs, including creating a peptide that makes tumors more porous and improving penetration of cancer medicines into solid tumors.
Efforts like the work being done at Sanford- Burnham don't occur in a vacuum, and they aren't validated without plenty of financial backing to ensure the efforts continue.
At the University of Chicago, Dr. Richard L. Schilsky is a professor of medicine and chief of the hematology/oncology section in the Department of Medicine. When it comes to money, Schilsky notes that for biomedical research, the main funding comes from NIH.
"For cancer research, the largest component of that comes from NCI," he adds. "The University of Chicago also receives funding from the Department of Defense, the National Science Foundation, a whole range of foundations and some other, smaller granting agencies."
And funding is an issue regardless of location. Across the Atlantic Ocean at the Institute of Cancer Research (ICR) in London, the pursuit of research funding is a vital effort.
The ICR is Europe's leading cancer research center, and has been ranked the U.K.'s top academic research center, based on the results of the Higher Education Funding Council's Research Assessment Exercise.
According to ICR's director of enterprise, Dr. Susan Bright, "Our funding is a mixture of government grants, grants from cancer and other medical research charities, funds raised from our own fundraising and some income from commercial partners."
On the other side of the funding table is the Cancer Research Institute. Founded in 1953 and based in New York, the institute is a nonprofit, charitable organization that raises funds for cancer immunology research from individuals, corporations and foundations. It provides direct support to cancer scientists through fellowships, grants and awards.
Brian M. Brewer, director of communications for the Cancer Research Institute, notes that the organization has funded research at more than 130 U.S. academic institutions in 31 states since 1974, including many state universities as well as the NCI and National Institute of Allergy and Infectious Disease (NIAID).
"We believe that each of them is excellent," he says. "As our focus is increasingly on the translation of basic immunology discovery into immune system-based therapies for cancer patients, our attention is primarily on those sites that are carrying out groundbreaking clinical tumor immunology and immune monitoring studies, or are focused on tumor antigen identification and characterization, in-situ tumor immunology and other aspects of human tumor immunology."
Funding enables academia to make strides in the fight against cancer, and Schilsky says the University of Chicago has laid the foundation for the development of targeted therapies for cancer.
"We did that from two different approaches. One is the development of all hormone therapy for cancer dating back to Dr. Charles Huggins' work in the 1930s demonstrating the importance of androgens to the growth of prostate cancer and the potential control of prostate cancer through removal of the testiclesófor which he won the Nobel Prize," he says. "That was the first convincing demonstration that hormones are responsible for control of a form of cancer. In the 1950s, there was the related discovery of the estrogen receptor by Dr. Elwood Jensen, providing the first molecular biomarker that has been used ever since to guide therapy for breast cancer. We know that women who have hormone response to breast cancer have a completely different prognosis and therapy pathway than women who don't have estrogen or progesterone receptors in their tumor."
The second prong to the targeted therapy, notes Schilsky, is Dr. Janet Rowley's work in the early 1970s showing that cancer is fundamentally a genetic disease, that the chromosomal abnormalities that occur in many cancers are not just random breaks in the chromosomes, but actually part of the pathogenesis of the cancer.
In what many term the era of targeted therapy for cancer, studying at a premier academic institution can certainly enhance an individual's career opportunities. It also can put them at the forefront in the race for a cure.
According to Prof. Paul Workman, head of Cancer Research U.K.'s Center for Cancer Therapeutics at the ICR, the facility not only plays an important role in discovering new cancer genes and figuring out how they cause cancer, but also in actually discovering and developing drugs based on the new molecular targets that emerge from this work.
"We take approaches that are commonly seen as too risky for the pharmaceutical industry," he explains. "Therefore, we are able to 'derisk' projects for industry, for example, by showing proof-of-concept in a lab model or in patients."
Schilsky notes that the basic scientists in academic centers are vitally important for target discovery.
"The basic scientists identify the molecules and genetic abnormalities that drive the formation of cancer. Those molecules and genetic abnormalities become the drug targets," he says. "What pharma is really good at is what might be called target validationódeveloping molecules or drugs that aim to hit the target. Pharma wants to develop drugs against validated targets, and it is up to our scientists in academic centers to discover those targets. It's a two- way street. I've known people who have worked a majority of their careers in pharma and have come back to academia and vice-versa. Once success is achieved in the lab, academic research centers must venture outside the walls of academia to select commercial partners to take their findings from the dish to the market."
Schilsky says the selection of commercial partners is driven by a number of things, but it's mainly the scientific interests of the faculty at the academic center and how those interests align with the product development pipeline of the company.
"For example, at the University of Chicago, Dr. Ravi Salgia is a world expert in MET signaling," he says. "Virtually every company that makes inhibitors to the MET pathway wants to work with him and tap into his expertise. Ravi has an interest in testing those inhibitors in the clinic because if he can demonstrate that a drug that targets the MET pathway is actually effective in treating cancer, it validates his own basic research."
At the ICR, Bright says a key objective is to find a commercial partner that will have the resources and the ability to develop their products and take them to marketóthus being sure that our discoveries reach as wide a patient population as possible.
"This is our primary aim, we do not select based on who pays the most - although of course we aim to get a fair commercial deal," she says. "If the relationship with the commercial partner begins early, during the drug discovery phase, then we would go through a period of collaboration. In this case, it is important to find a commercial partner that can bring resources and skills that complement our skills, creating an effective project team."
With such a rich history behind it, academia's role in the future of cancer research seems to be entrenched. As Brewer explains, academia has always played a critical role in cancer research and will continue to do so.
"In the field of tumor immunology, in particular, we believe that organizations like the Cancer Research Institute can help to bridge the divide between academic, discovery-driven research and industry, product-driven drug development, primarily by providing funding for early stage, combination drug trials," he says. "Such trials would be designed to answer specific scientific questions while also finding ways to optimize the therapeutic benefit a new drug might ultimately have on patient health (by combining it with other drugs, for example). To that end, we have developed a new Cancer Vaccine Acceleration Fund, which is designed to catalyze the development of promising cancer immunotherapeutics. In exchange for our provision of funding to industry partners, we secure access to their proprietary drugs for academics to use in combination trials."
CRI's goal is to ensure that any company sitting on a potential new cancer therapy has the capital to run clinical trials of that therapy in a cancer indication within its coordinated academic clinical trials network.
"In this way, we extract maximum immunological knowledge from each trial, analyze its results within a global framework, and potentially help to inform the design of new combination approaches to cancer immunotherapy that will be of greater benefit to more cancer patients," Brewer says.
The last 100 years has seen an explosion of advancement in the arena of cancer research, and it may only be the beginning of advances that were not even imagined a few years ago. Academia will continue to play a key role.
"In many academic research facilities, certainly at the University of Chicago, cancer is the centerpiece of the research and clinical enterprise," Schilsky says. "There are more than 60 NCI-designated cancer centers in the country and they are all at academic facilities. Academic facilities are the key drivers of the cancer research portfolio of the United States, ranging from basic discovery research, through translation, to clinical trials, to population research."
Moreover, he concludes that cancer continues to be a major public health problem and remains a major interest to fundamental scientists because of its biological complexity.
"There are many cancer patients who are still seeking innovating clinical trials and multidisciplinary care that academic centers are particularly good at providing," he says.