Scholar Research and Accolades
Our scholars and their research are where the vision and work of ARCS Foundation Oregon are realized. The members of the Oregon Chapter are proud of our scholars and delighted to record their progress and success.
David Edwards Researches Acute Myeloid Leukemia Through Precision Medicine
David Edwards, a third year ARCS scholar at OHSU, is researching the most deadly form of blood cancer called acute myeloid leukemia, or AML. He is working at the genetic level to identify the mechanisms of chemotherapy resistance. While there’s so much fascinating research being done on AML at OHSU, David’s research is involved with something called “precision medicine”.
What exactly is precision medicine? To answer that question, especially in the context of cancer, the discussion should start more broadly: What is cancer?
David heard a science reporter on the radio answer this very question: “Think of cancer as an alien life-form attacking your body. The cancer cells have undergone such radical transformation that they hardly resemble normal cells anymore. Imagine cancer as some perverse Frankenstein’s monster, born of corrupting mutations in their DNA and ravaging the surrounding countryside of normal tissue.”
While David liked this comparison, he didn’t think it went far enough. Cancer is much more insidious and calculating. So, David describes another analogy: “Let’s think of your body as a gigantic corporation—and yes, for the sake of argument, corporations are people too. And cancer, in my opinion, is a disgruntled employee. Maybe he’s embezzling the company funds; maybe he’s stealing snacks from the break-room. Ultimately, cancer is trying to take down the company—your company—by whatever means necessary.” He continues his thought, “Because, you see, cancer is an insider. Cancer knows all your tricks. He’s read the company memos, knows your corporate handbook. He knows exactly how you’ll respond to his actions, and how to overcome it.”
What does this mean biologically? Cancer makes the body work against itself. It can convince nearby cells to secrete growth factors against their will. And if you send in the immune cavalry, not only can cancer evade their detection, they can also recruit these immune cells for its own nefarious purpose.
So the question becomes: How do you target such an enemy?
David explains, “For cancer, we use chemotherapy. But most of our chemotherapies are non-specific. They go after all rapidly dividing cells in the body. This includes cancer cells, but also hair cells, intestinal cells, etc. It’s the equivalent of firing the entire fourth floor to get rid of one employee, or canning everyone in HR. Precision medicine is different. It targets the person directly—what’s his name, where exactly does he work. What makes him unique.”
In David’s research, he studies each leukemia individually—learning its background, identifying its causal mutations. Then he uses small molecules that bind only to those mutated proteins. This kills the cancer cells while leaving normal cells unharmed. Brian Druker, one of the pioneers of precision medicine, famously “beat” one type of leukemia using a drug that targeted a gene mutation found only in that leukemia. This is the new paradigm for cancer treatment, a new way of targeting the disease. And while the notion of “curing” cancer is extremely ambitious, David believes that research into precision medicine will unquestionably help patients live longer, healthier lives.
David thanks ARCS Foundation saying, “Without question, the support I have received from ARCS, and in particular from my donors Sharon and Henry Hewitt, has been indispensible during this critical time in my research career. I cannot thank ARCS Foundation enough.”
Lillian Klug Developing Novel Therapies for Treatment of Chemotherapy and Radiation Resistant KIT-Mutant Cancers
Cancers are generally caused my mutations in the DNA that cause otherwise normal cells to behave abnormally and grow uncontrollably. For many cancers the exact DNA mutations that cause cancer are not known. However, there are some cancers that are caused by single specific mutations.
In the lab of Dr. Michael Heinrich, Lillian studies cancers caused by mutations within a single gene called KIT. KIT is a gene that is important for development - it functions by sensing growth signals and tells cells to grow inappropriately. The growth signals stop in adulthood, so the cells stop growing. In the case of cancers, such as GI stromal tumor, melanoma subtypes, and mast cell leukemia, however, mutations within KIT cause it to function again, even in the absence of growth signals and the cells start growing uncontrollably. Fortunately, because we know what causes the cancer to grow, we know how to stop it from growing.
There is a drug that can inhibit the function of mutant KIT and prevent it from telling the cells to grow inappropriately. This drug is called Gleevec, and it is a targeted therapy. Gleevec has revolutionized the treatment of cancers caused by KIT mutations, because many of these cancers are chemo and radiation resistant. On Gleevec, now some patients have survived decades, where previously it was mere months. However, Gleevec is a chronic therapy and patients must take it every day. This means it is not truly a cure, because not all of the cancer cells die. Some cells can survive pressure of the drug and are merely kept from growing, but if the drug pressure were removed they would grow back.
Lillian’s work is to understand the survival mechanisms that these cells use and find ways to target the survival pathways in combination with targeting KIT with Gleevec to kill more cancer cells. She is using drug library screening to identify drugs that target survival pathways in cancer cell lines. Many of these drugs are FDA approved and, once identified, can move swiftly into a clinical trial setting. Lillian is very motivated by the fact that her work may help improve outcomes of people suffering with KIT-mutant cancers.
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