Project Spotlight

Our faculty are conducting research that leads to breakthroughs in cancer research. Their findings are publicized in high-impact journals, news media and textbooks. The following are brief summaries of selected research projects:

Drug Sensitivity Trials for Leukemia
Funded by NIH
Led by: Pamela Becker, MD, PhD

Dr. Pamela Becker
Dr. Becker

Everyone’s cancer is different; a one-size-fits-all approach to treatment simply is not good enough. In order to change outcomes for people with cancer, we need to rethink how we treat cancer at an individual level. Using precision medicine, we can develop new drugs based on an individual’s biology and tailor treatments to someone’s specific cancer.

At present, approved specialized drugs exist for only a fraction of cancer-causing mutations, and these mutations for which we have specific drugs are found in a very small fraction percentage of all cancer cases. In order for precision medicine to fulfill its potential as a powerful cancer-fighting tool, more data on the genetic mutations that lead to cancer and contribute to resistance to chemotherapy drugs must be gathered. Also, the drugs needed to treat each mutation must be developed. This is exactly what Pam Becker, MD, PhD and her team at UW Medicine are doing with the help of the Institute for Stem Cell and Regenerative Medicine.

Currently, Dr. Becker is conducting a clinical trial for adults and children with acute leukemia, in which the tumor cancer cells have resisted the original treatment. This clinical trial takes into account patient information on gene mutations, gene expression and in vitro testing. Tumor samples collected from individual patients will be screened against drug compounds and drug combinations. Using this process, our researchers determine which drugs — or combination of drugs — will be most effective to treat cancer within the individual patients. This exciting approach has the potential to speed the selection of personalized treatments, making the process more cost effective than traditional treatment methods.

This work has exciting implications, especially for people with leukemia. By treating patients with the therapies that will have the best response to their disease, patients will have the greatest chance of a positive outcome. While the results of both these trials are highly specific to AML and multiple myeloma, developing this model of precision-medicine research will be a fundamental step in driving forward similar approaches in other cancers.

Response and relapse in hematologic malignancies: The Biology of Luck
Funded by
Led by: Jerald Radich, MD

Dr. Jerry Radich
Dr. Radich

Why do some people respond to therapy and others do not? We often call this “luck”, but what is the biology behind this phenomenon? This issue is really at the heart of what people call “personalized” or “precision” medicine-the hope that somehow understanding the science behind treatment response will help us to tailor therapy for each patient. The study behind understanding response is difficult as we now know that tumors are not a collection of identical cells, but instead genetically similar but unique clones that can compete against each other as well as against normal cells. Thus, the battle in cancer is not just normal cells versus a cancer, but the competition between the cancer cells. Each patient is a very complicated ecosystem, governed by natural selection as the clones fight for resources.

Most types of cancer respond to therapy at first and then relapse. This may well be the elimination of one cancer clone, which gives a competing clone an advantage. The clone that is the majority may not be the one that is driving the illness. Thus, in many cases, studying the mixture of cancer will be misleading. An alternative approach is to look at the patients who do spectacularly well, or poorly, purposely biasing the study towards the extreme responders. In addition, we can learn about how clones compete by studying the genetics of single cells. Examples from our lab can underscore how these are potentially interesting and rewarding approaches.

Non-responders in AML. In this study we have performed wide-scale genetic analysis on normal AML, comparing 100 patients with no response to 100 patients who enjoyed a long-term remission after standard therapy. The aim is to develop a diagnostic test that will predict initial response to therapy, as well as identify to targetable pathways that will allow non-responders to be treated with novel agents to make them responders.

Early molecular response in CML. Drugs known as tyrosine kinases have changed the natural history of CML, and are the standard treatment. Still 15-30% of patients show no response after 3 months of treatment. We are comparing patients who have a poor initial response compared to those with a dramatic 3 month response, to understand the biology responsible for early response. As above, these studies should yield diagnostics to predict response, and an understanding of potentially targetable pathways to influence response.