By: Rachel Black
Pancreatic cancer is the deadliest of all cancers, yet pancreatic cancer research is significantly underfunded. Dr. Channing Der, Kenan Distinguished Professor in the Department of Pharmacology at the UNC School of Medicine and UNC Lineberger Cancer Center Member, is working in the lab to develop new therapeutic strategies to treat pancreatic cancer. Dr. Der is also very passionate about raising awareness and funding for pancreatic cancer, which is internationally symbolized by the color purple.
According to the American Cancer Society, the five-year survival rate for pancreatic cancer is 7%, the lowest for all major cancers. 74% of patients will die within the first year of being diagnosed. For most, a diagnosis of pancreatic cancer is a death sentence. Current therapeutic approaches are largely ineffective, and survival rates have not substantially increased in over forty years. In the words of Dr. Der, “We need to try harder. We need to do a better job of finding ways to treat this disease.”
Over three decades ago, Dr. Der was an integral part of the discovery of the RAS family of oncogenes in human cancers (Figure 1). Der explains, “The majority of cancers arise through mutations in our own genes, and the highest frequency of mutations are in the three RAS genes.” In fact, 25% of all cancers have mutations in one of the RAS genes, which Der helped identify, that cause the gene to be chronically active. It is alarming that there are no therapeutic strategies that target RAS oncogenes given that no other mutation in cancer is as common. RAS mutations are even higher in pancreatic cancer, as an astonishing 95% of pancreatic cancers have a mutated KRAS gene, which is in the RAS family. Given the significant disease burden that pancreatic cancer presents, Der views this as an opportunity to address how new therapies can be utilized to treat this rampant, seemingly unstoppable disease that has taken the lives of 40,560 people in the last year.
With the assistance of grants from The Pancreatic Cancer Action Network and the American Association for Cancer Research, the Der Lab has recently developed a promising new drug, classified as an ERK inhibitor, which turns the mutated KRAS gene off. This approach is one that hasn’t been attempted before, but has shown significant promise in the lab and in preclinical studies. The signaling protein ERK is essential for tumor metabolism in pancreatic ductal adenocarcinoma. While there are other ERK inhibitors on the market, they have proven to be largely ineffective. These unsuccessful ERK inhibitors target the first and second steps of the three-step pathway RAF-MEK-ERK. Cancer cells are able to overcome existing inhibitors and turn the pathway back on. The ability of cancer cells to thwart the inhibitors and reactivate the pathway indicates that the ERK signaling pathway is essential in the proliferation of cancer cells. Unlike the others, Der’s ERK inhibitor targets the last step of the pathway. Cancer cells have a much harder time overcoming this block, and recent studies suggest that this method is effective, Der says.
It is important to note that this is not a drug that will alone successfully treat all cases of pancreatic cancer. Combination therapy is the most common drug based treatment for cancer, in which drugs are combined in ways that attempt to prevent the cancer from becoming resistant. Since cancer cells grow and divide at such a fast rate, it is easy for them to become resistant to target drugs and this is often why the success of drug therapy differs from patient to patient. Der and his colleagues have identified combinations to work in tandem with the previously mentioned ERK inhibitor, and are testing these combinations in mouse models. Der hopes that they will go to clinical trials soon.
Though Dr. Der works vigorously in his lab at the UNC Lineberger Center, he also finds time to make a difference in the lives of those affected by pancreatic cancer outside the lab. He regularly attends trips to Washington D.C. alongside families who have lost a loved one to pancreatic cancer to lobby for more funding for pancreatic cancer, which is largely underfunded by the federal government. According to a report released in 2010 by the Pancreatic Cancer Action Network, pancreatic cancer receives a meager 2% of National Cancer Institute funding, while the other four of the top five deadliest cancers receive two to six times as much funding. Looking at N.C.I. funding in amount per death reveals a huge disparity: pancreatic cancer receives the second to lowest amount of funding per death at $2,297, while breast cancer has the highest at $13,452 (lung cancer has the lowest). Thankfully, the visits to senate and representative offices in Washington D.C. paid off, literally, in 2013 when the Recalcitrant Cancer Research Act was passed. As a result of this act, more funding was allocated and strategic plans were put in place to make progress in treating deadly cancers. Additionally, groups such as Purple Stride are working tirelessly to raise awareness and encourage education, research and fundraising for the disease. Two undergraduates who work in the Der Lab, Christina Kresser and Daniel Zeitouni, founded Purple Mission at UNC to expand this focus right here on campus. And they have made a difference. Pancreatic cancer research funding has increased by 500% since 1999 thanks to groups such as these and advocators everywhere.
In cohort with Purple Stride, the Der Lab hosts open house events in which they open their doors to the community and people can come into the lab and see what research really looks like, view live pancreatic cancer cells and observe research techniques. These events not only raise awareness and educate people about pancreatic cancer, but also give members of the community who have been affected by pancreatic cancer a sense of hope that one day there will be a successful treatment. Der believes that the humanitarian side of his research provides he and his lab members with additional motivation to pursue an effective therapy. Der explains, “What we’re doing is supposed to make an impact. We’re not getting grants simply because were finding out cool things. We’re getting grants because what we find hopefully can be applied to develop better approaches for cancer treatment and care.”