Dr. Malachi Griffith – Research in Action
Read moreType: Translational
Facilitate the transition of projects from the laboratory to the clinic. Translational researchers seek to apply basic knowledge of cancer and bring the benefits of the new basic-level understandings to patients more quickly and efficiently. These grants are $600,000, three-year commitments
Alice Shaw, M.D., Ph.D., Jeffrey Engelman, M.D., Ph.D.
Anna R. Giuliano, Ph.D., Soner Altiok, M.D., Ph.D., Gerold Bepler, M.D., Ph.D., Douglas Cress, Ph.D., Hui-Yi Lin, Ph.D., Matthew B. Schabath, Ph.D.
Suzanne J. Baker, Ph.D., Cynthia Wetmore, M.D., Ph.D.
John V. Heymach, M.D., Ph.D., Varsha Gandhi, Ph.D., Christine Stellrecht, Ph.D., Carlo Toniatti, M.D., Ph.D., Timothy Heffernan, Ph.D.
Tanja A. Gruber, M.D., Ph.D., James R. Downing, M.D.
Benjamin L. Ebert, M.D., Ph.D., Ann Mullally, M.D., William Kaelin, Jr., M.D., David Steensma, M.D.
Gianpietro Dotti, M.D., Cliona Rooney, Ph.D., Caridad Martinez, M.D.
Michael Weber, M.D.
“Precision medicine” aims to develop better treatments by understanding the molecular causes of disease. This is essential in cancer because each type (breast, brain, or blood cancer, for example) represents dozens of different kinds of cancer at the molecular level. And each of these different molecular sub-types requires different treatments.
Based on research of the past twenty years, we understand a great deal about what drives cancers. Many drugs have been devised that specifically target these causes – molecular “smart bombs.” However, the cancer cells rapidly adapt and find escape routes. Drugs that seem to work ultimately fail. We get many hopeful responses but few cures.
Our research seeks to identify and block these escape routes. We look at the molecular changes inside cancer cells after drugs are applied, and we then use other drugs to “slam the door” so the cancer cannot escape treatment. Our approach is already proving successful: We are testing one of these combinations in people to treat Mantle Cell Lymphoma. We propose to look at similar cancers that might benefit from this approach. We also want to better understand ways that cancer cells might escape from our combination treatments. Our goal is to improve responses to therapy and turn temporary responses into real cures.
David Tuveson, M.D., Ph.D.
Pancreatic cancer is one of the deadliest cancers, largely because most therapies are poorly active in patients or are too toxic when administered. Indeed, pancreatic cancer patients become ill very quickly, and cannot withstand the side effects of chemotherapy that patients with other types of cancer can tolerate. Therefore, we need to identify new therapies that kill pancreatic cancer cells effectively and are well tolerated by patients. To accomplish this goal, we have developed a new model system from pancreatic tumors, called organoids. Organoids are 3D cultures grown in an extracellular material rich matrix, called Matrigel, and can faithfully mimic the patient’s tumor, from which it was derived. Organoids can be used to sequence for mutations in the cancer cells and to test for therapies that could kill the cells. Using organoids, we have identified a number of compounds that can surprisingly kill the different cell types present in pancreatic tumors, including several drugs that are given to millions of people daily and are well tolerated but not previously considered to be cancer medicines. Importantly, we also find that certain combinations of these new drugs can shrink human pancreatic tumors engrafted in mice. Here, we propose to extend these exciting preliminary findings to a broader collection of drugs and a larger collection of organoids, and develop the most promising candidates as new strategies for an early phase clinical trial. Our goal is to test at least one novel combination of non-traditional drugs in pancreatic cancer patients within three years.
