Volume 1, Issue 1 Fall 2003
|Inside This Issue
Interview with Dr. Charles Sawyers
What's On Your Mind: Questions from our Readers
Coming Up in Advance
WHAT'S NEW AT ABC2|
It is with great pleasure that we bring you this first edition of ADVANCE, our quarterly newsletter. This newsletter will highlight the work of different researchers who are recipients of ABC2 research awards and keep you informed of their pivotal discoveries. The search for improved therapies for brain cancer presents a compelling challenge to the scientific and medical community – the unmet medical need is tremendous and the technological know-how and clinical tools are rapidly advancing.
So compelling is this challenge that Dr. Charles Sawyers, world-renowned cancer specialist, has chosen to expand his research efforts into the brain cancer field and has become an ABC2 investigator. We thought it would thus be fitting to feature him in this inaugural issue of ADVANCE to explain what specifically drew him to the field and where he believes the research is headed. We hope you enjoy reading the newsletter and appreciate your comments and suggestions for enhancement.
|ABC2 Progress in 2003
IN PURSUIT OF A CURE|
News from ABC2 Investigator Charles Sawyers, M.D.
Landmark clinical studies in chronic myeloid leukemia (CML) of a new small molecule drug, Gleevec® (Novartis), were reported in 2001. This drug produces dramatic clinical responses with minimal toxicity in CML. Gleevec, which was approved by the FDA in less than three months, has become a first line therapy and has revolutionized the treatment of CML. Gleevec works in CML patients whose cancer is attributable to a particular molecular abnormality that leads to improper functioning of a kinase (an enzyme involved in regulating cell growth and proliferation).
ABC2: You have made tremendous contributions to the treatment of prostate cancer and leukemia. Why did you expand your research into brain cancer?
Dr. Sawyers: There are several reasons. For one, there is great scientific rationale for it. There are solid data demonstrating that the molecular abnormalities found in approximately 50% of brain cancer patients are precisely the kind that are amenable to the kinase-inhibitor approach proven to be successful in leukemia with Gleevec. Also, in brain cancer, we have ready access to tissue from patients’ tumor biopsy for study and, unlike many other cancers, imaging techniques provide us with a very accurate picture of the status of tumor growth. Thus, we can see the direct effect on the cancer cells as a result of treatment, which is critical because it helps to determine if the drug we are testing is affecting the molecular pathways we want it to target. Having that kind of information accelerates advances and optimizes the treatment strategy.
ABC2: What more needs to be done with targeted therapies for brain cancer?
Dr. Sawyers: I am convinced that the best application of this kind of therapeutic intervention in solid tumors is in the treatment of brain cancer. We must continue to develop methods for identifying some of the key molecular players involved in initiating and maintaining the growth of brain cancer cells. However, not all molecular players are clinically useful – it depends on the degree to which targeting that particular player will differentially affect the growth of cancer versus normal cells. Thus, a lot of work needs to go into validating the molecular targets for clinical utility. Also, I believe that it is vital to test promising drugs in clinical trials in parallel with studies being conducted in the laboratory, so we can draw definitive conclusions from the data and thereby make significant advancements each step along the way to finding a cure.
ABC2: How do targeted interventions with kinase inhibitors differ from chemotherapeutic drugs?
Dr. Sawyers: Chemotherapeutic drugs do not produce impressive responses in brain cancer and that is primarily because they are not very discriminatory in their effects. They produce damage to the normal cells, a phenomenon which we term the “bystander effect.” Therapy with a kinase inhibitor, on the other hand, targets an abnormality that is unique to the cancer cell and therefore the drug’s killing action is confined to the cancer cells.
ABC2: We often hear that cancer cells can develop resistance to therapy. Can that also happen with this new class of kinase inhibitors?
Dr. Sawyers: Yes, but even so, we know so much about the process by which that happens that we are confident that we can address resistance with the use of combination therapy – just as we currently do to avoid antibiotic resistance.
Dr. Sawyers: The field is headed towards customized therapy driven by a rational selection of drug combinations. I expect we will start testing combination therapies in the next year or two. There is increasing recognition that all cancer is a disease of molecular pathways that regulate cell growth and division. We still have a lot to learn about how to use kinase inhibitors safely and how to use them in optimal combination. The key will be to recognize which one of the several possible pathways is disrupted in particular patients and to treat accordingly. In the future we will have a drug that is designed to interfere with a particular pathway that has gone awry in the cancer cell and is responsible for its continued growth. The same signaling pathway may be disrupted in cancers originating in different organs. So the key clinical element that will determine which drug regimen to give a patient will be the molecular lesion exhibited by that patient’s cancer cells. That’s where the concept of customized medicines comes into play in cancer; and that’s how a major discovery in the treatment of leukemia can create such excitement for the potential treatment of brain cancer. The particular molecule in a kinase-regulated pathway that is disrupted in brain cancer cells is distinct from the one exhibited in leukemic cells. However, the proven strategy of inhibiting aberrant kinase activity using a small molecule drug applies to both!
WHAT'S ON YOUR MIND: QUESTIONS FROM OUR READERS
Dear ABC2: Do you keep track of the progress achieved by recipients of the ABC2 individual research grant awards?
Yes, we do. Once we’ve designated which projects we will fund, we get together with the principal investigator to set specific project milestones. Over the course of the year, we keep track of the progress being made and help troubleshoot any way we can when unexpected stumbling blocks arise along the way. As is the nature of things in science, there are delays, but by and large, projects are completed within a few months of their projected completion date.
If you have any questions or comments please send them to: [email protected] or ABC2, ADVANCE Newsletter, 800 Airport Blvd, Suite 508, Burlingame, CA 94010.
COMING UP IN SUBSEQUENT ISSUES OF ADVANCE:
The "In Pursuit of a Cure" segment of our newsletter will feature news from ABC2-sponsored investigators on such topics as:
©2003 Accelerate Brain Cancer Cure