Moderator: Michael W. Smith, MD
Roundtable participants: Lewis C. Cantley, PhD (Harvard Medical School); Peter Jones, PhD (University of Southern California); Dennis J. Slamon, MD (UCLA’s Jonsson Comprehensive Cancer Center). Read more about the researchers and their teams’ work.
"This is where the end of cancer begins."
That is the mantra and the mission of Stand Up To Cancer (SU2C), the powerhouse advocacy organization founded last fall to raise money to kick-start cancer research. SU2C got off to a splashy, star-studded start with a primetime TV show and fundraiser. Then, just nine months later in May, SU2C had raised enough money to award nearly $74 million to five U.S. cancer research teams (dubbed "dream teams") involving more than 200 researchers from 20 leading institutions. The goal? To work together in a more collaborative way to speed effective new treatments from labs to patients as quickly as possible.
Cancer is still a formidable foe, despite decades of research. The cancer death rate has decreased over the last 15 years, but cancer still claims entirely too many lives: According to the American Cancer Society, more than 560,000 people will die of cancer in 2009.
Taking a multidisciplinary, integrated approach, SU2C proposes to reduce some of these numbers by changing how cancer is researched. To find out more, WebMD talked to three dream team leaders -- find out more about them below -- about their projects, how they plan to use the grant money, and what their work will mean for cancer patients -- with luck, sooner rather than later.
Q: What makes the SU2C research model so different for cancer research?
Cantley: This new approach to funding as well as the researchers' collaborative approach [means] there is sufficient money to put together teams across institutions and still have enough so people can actually reach their goals. We can bring in people who have very strong expertise in different fields to share the money and their expertise.
Dr. Jones: In addition, it allows people to draw up collaborative arrangements with their colleagues and competitors much more quickly than is usually the case. With this initiative, there was a clear urgency to get the right people together as quickly as possible.
Dr. Slamon: We all believe in this model, and I agree that it is unique in demanding a multi-institutional approach of experts. Also, the team leaders will be interacting among teams where there is obvious overlap, sharing information across teams, not just within teams.
Q: Dr. Cantley, your area of research is the PI3K "pathway," a process that leads to cancerous cells growing and surviving. What exactly are you studying?
Dr. Cantley: As you note, the pathway itself controls cell growth and survival. "PI3K" is actually an enzyme that is the central player in that pathway. Research has confirmed that the P13K pathway is perhaps the most mutated pathway in all of cancer, and especially in women's cancers. So what's exciting is that [it may be] possible to make a small molecule that you can take as a pill orally that would turn off the enzyme's function and thereby stop the growth of the cancer. That could be potentially useful in treating the disease.
We are designing clinical trials to test that idea in multiple types of breast cancers. We're looking at endometrial and ovarian cancer, too. We know, for example, that the enzyme is frequently mutated in endometrial cancer and in estrogen receptor-positive breast cancer.
Q: What are you hoping will ultimately be the outcome of your ongoing research?
Dr. Cantley: The outcome, I think, will be accelerated approval of these drugs, and teasing out which drugs should go forward in clinical trials and which people ought to be in those trials. If we could actually predict with some 90% probability who is likely to respond, the phase III stage [final trials designed to lead to a drug's approval] could be very rapid, and we could get drugs out onto the market in four or five years. Currently, these drugs are only in phase I trials to evaluate toxicity and optimal doses.
Q: Dr. Jones, your group is studying "epigenetics," which looks at how certain genes are used by certain cells and then how and why the genes get turned on and off. Sometimes these processes go awry and cause cancer. What does your research entail?
Dr. Jones: Dr. Cantley just described mutations in key pathways that lead to disruptions in cellular control, meaning the cell behaves in an abnormal fashion. With epigenetic processes, we're more interested in the packaging of the genes within a cell. There may be a perfectly good gene in the cell, but it's switched off in a way that the cell cannot use it. These genetic changes can cause the development of cancer.
The current approach is to use drugs that are capable of turning the genes back on. The hope is that by doing so we can restore the normal pathways that have been extinguished in a particular cell type.
What our team is trying to do is figure out why the drugs work in some people and not in others, and to extend the reach of these approaches from blood cancer -- where it is already being used -- into solid tumors, focusing initially on lung cancer and also on breast cancer.
Q: Are there clinical trials that are ongoing now, and what are they looking at specifically?
Dr. Jones: Yes, several clinical trials are targeting the epigenetic process in different types of cancers, particularly using the idea of combination therapies, where you target multiple steps in the process that abnormally silence the genes.
One of our team's goals is to develop a clinical trial to test a new and improved drug that more effectively blocks the epigenetic changes that can lead to cancer.
Also, we want to develop biomarkers, which are substances that can predict and monitor the effectiveness of these epigenetic treatments, to get a sense early on if they're working.
Q: Dr. Slamon, your project focuses on breast cancer "molecular subtypes," which refers to the relatively new knowledge that most cancers are not just one disease. Instead, they can be one of many different subtypes or varieties. What is the significance of your research?
Dr. Slamon: We know there are probably at least seven major molecular subtypes of breast cancer -- plus subgroups within those subtypes. Up to now, we've been taking a one-size-fits-all approach to treating a diverse disease. The result is that we have limited ourselves in our ability to effectively treat it.
So our team was put together knowing that we've made some inroads by applying the right cancer therapy to the right group with a particular type of cancer subtype. Now we want to take it much further and try to understand how molecular alterations in each subtype respond to which therapy so we can really refine and improve treatments for patients.
Q: It seems that some of your teams' work is similar. Is there a chance for collaboration?
Dr. Cantley: Yes. Some of the teams actually had overlap in terms of who they invited to work with them. These people had to go with one team or the other, but as we go forward, they will help the teams communicate with one another.
Dr. Jones: It's important to remember, too, that this can all feed into the idea of "combination therapies," where you target multiple steps in the processes that can lead to cancer, instead of just aiming at one step with one drug.
Dr. Slamon: The whole objective is to move good ideas being developed in the laboratory into the clinic, where they can be evaluated more rapidly. This is a very exciting model for research, and if it works I suspect it'll be something that's done more and more.
Meet Our Stand Up to Cancer Researchers
Lewis C. Cantley, PhD
Team: Targeting the PI3K Pathway in Women's Cancers
Grant: $15 million
Goal: To determine which patients will respond positively to treatments that target mutations in a set of genes that regulate a certain cellular "pathway" in the body. Breast, ovarian, and endometrial cancers all have this pathway.
Peter Jones, PhD
Team: Bringing Epigenetic Therapy to the Forefront of Cancer Management
Grant: $9.12 million
Goal: To study epigenomes, layers of material outside of DNA in cells that can lead to cancer by turning genes on and off -- and ultimately to discover medicines to combat these molecular changes. The team will focus on breast, colon, and lung cancers, as well as leukemia.
Dennis J. Slamon, MD
Team: Integrated Approach to Targeting Breast Cancer Molecular Subtypes
Grant: $16.5 million
Goal: To better understand breast cancer's molecular diversity (since not all breast cancers are the same) and to develop treatments tailored to specific "subtypes" of the disease.