Cancer is crafty. The disease often resists treatment and developing long-lasting, effective therapies is a challenge. University of Colorado Cancer Center investigator Craig, Jordan, PhD, has been awarded a $5 million grant to build on his body of work targeting cancer stem cells which may mean improved treatments for thousands of people with a particular kind of leukemia.
The grant comes from the Leukemia & Lymphoma Society, the world’s largest nonprofit devoted to curing blood cancers. Jordan and his colleagues were awarded a Specialized Center of Research (SCOR) grant to put together a multi-disciplinary team of researchers to produce long-term disease control in patients with acute myeloid leukemia (AML).
“Our work in AML could change the way clinicians think about this disease,” says Jordan. “Outcomes in AML are dismal, and the standard treatments have major side effects affecting quality of life. We believe the lack of progress in AML is because we have been attacking leukemia cells when we should be concentrating on the root of the disease – leukemia stem cells.”
Jordan, chief of CU Department of Medicine’s Division of Hematology, and collaborators at CU Cancer Center are taking a multi-pronged approach to eradicate cancer stem cells in patients with AML.
The main components of Jordan’s multi-disciplinary approach are:
- Targeting AML stem cell metabolism: The focus of Jordan’s SCOR project is to develop drugs that kill AML stem cells by blocking their ability to produce energy. This strategy has recently been tested in AML patients, where it achieved extraordinarily promising initial results. In a trial conducted at the University of Colorado, 91% of AML patients achieved a complete remission. In addition, the treatment was much less toxic than chemotherapy, improving patients’ quality of life while undergoing treatment.
- Using the immune system to attack AML stem cells: Terry Fry, MD, leads this project, which leverages the newly emerging field of immunotherapy. Fry is among a small group of pioneering scientists who have shown that a patient’s own immune system can be trained to kill tumor cells. Fry is designing new strategies to teach T cells from an AML patient to specifically target AML stem cells. He has previously demonstrated that this CAR T-based approach is highly effective for lymphoblastic leukemia, a close cousin of AML.
- Seed vs. Soil, using the tissue “ecosystem” to suppress AML stem cells: James DeGregori, PhD, Eric Pietras, PhD, and Michael Becker, MD will assess how surrounding tissues (i.e. the “soil”) influence the growth and survival of AML stem cells (i.e. the “seed”). In previous studies, they have shown that chemotherapy damages normal tissues in such a way that favors the growth of AML stem cells over that of normal stem cells. When this happens, tumor cells rapidly take over the patient’s healthy tissues, leading to disease progression and death. Our investigators will seek to identify new methods that do not damage the tissue “soil” in which AML and healthy stem cells reside.
- A “Land, Sea, and Air” attack on AML stem cells: This final project will integrate the concepts in projects #1-3 to conduct new clinical trials. A major limitation for therapies currently in clinical use is that no single agent has successfully targeted these diverse cells. Consequently, the simultaneous use of multiple, different strategies is an important tactic – Jordan calls it a “land, sea, and air” attack. The trials will be directed by Clayton Smith, MD, and Daniel Pollyea, MD, leading experts in clinical research for AML. Not only will this work provide new forms of therapy directly benefitting patients, but it also may devise better forms of diagnosis. Currently, there is no test that evaluates the characteristics of a patient’s AML stem cells. Consequently, physicians are not able to tailor therapies to the specific characteristics of their disease. A key component of the new trials will be to analyze each patient’s unique AML stem cell population, and then to customize their treatment accordingly. A patient’s therapy will be individualized to incorporate the advances achieved in projects #1-3, along with many other rapidly emerging strategies supported by other LLS-sponsored research teams.
Jordan and colleagues expect the outcome of the combined efforts will represent a new paradigm in the treatment for AML.
LLS awarded Jordan $2.5 million. Matching funds were provided by the University of Colorado School of Medicine, CU Cancer Center, CU School of Medicine’s Department of Pediatrics, and endowments from the Division of Hematology.