BROOKINGS, S.D. — April 26, 2023 — Noted cancer researcher Frank McCormick comes to Brookings Monday with good news concerning some traditionally hard-to-treat cancers.
McCormick, a distinguished professor of tumor biology and cancer research at the Diller Family Comprehensive Cancer Center, University of California, San Francisco, will deliver the 10th annual Francis Miller Public Lecture in Cancer Research at 7 p.m. in Bailey Rotunda F, 1020 Campanile Ave., on the South Dakota State University campus. It is sponsored by the College of Pharmacy and Allied Health Professions.
“It’s not going to be a cure tomorrow, but over the next decade it is going to transform the way patients are treated,” McCormick said.
His work deals with the Kirsten rat sarcoma viral oncogene. It is commonly known as KRAS (pronounced K-raz) and is the most frequently mutated cancer gene. It is found in a number of proteins commonly associated with lung, pancreatic and colorectal cancers. While KRAS normally helps with cell growth, having a mutation can tell cells to grow more than they need to. This overgrowth can lead to cancerous tumors.
The gene was discovered in 1964, but it wasn’t until 2012 that science knew enough about what the protein looked like to know how to attack it, he said.
Forms own research lab
“The protein is like a swishy tennis ball without any pocket for the drug to attach. Other cancer proteins are like a lock and key. In KRAS, there is no hole where drugs can bind. That has made drug development for the KRAS gene very challenging,” said McCormick, who formed Onyx Pharmaceuticals in 1992 to develop new cancer therapies.
That led to the approval of Sorafenib in 2005 for treatment of renal cell cancer and for liver cancer in 2007 and the approval of ONYX-015 in 2006 in China for treatment of nasopharyngeal cancer.
“In 2012 new technology made it possible to find compounds to bind to a squishy tennis ball. Then things picked up in 2013 when a colleague found a handle on a mutation of the protein, an amino acid residue. This reactive amino acid was the handle. That was a very specific solution, but it propelled research into more genes.
“There are four common residues that are mutated in KRAS. One of them makes a handle which drugs can bind to. But even drugs that haven’t been effective have helped with the learning process,” McCormick said.
Pharmaceutical stampede predicted
Two drugs have received final FDA approval for treatment of KRAS genes. “While these drugs are very specific to one form of the gene, there is a whole pipeline of drugs on the way. There are a lot of things coming down the pike. Patients should be optimistic,” said McCormick, who has led the National Cancer Institute’s RAS Initiative at the Frederick National Laboratory for Cancer Research since 2013.
While approved drugs target types of lung cancer, “20 drugs targeting the KRAS gene are in clinical trials. It’s a stampede.
“I see every pharmaceutical company pursuing some variance of these compounds, binding these drugs with a whole range of other drugs to make them less toxic to healthy cells and more effective. The whole industry is just developing, just getting started, and it will be like this for 10 years plus,” McCormick said.
In April he presented at the annual American Association for Cancer Research, a major conference in Orlando that drew 20,000 people.
“Sessions on KRAS were the ones best attended. KRAS was the most important theme of the meeting. In previous years, immunotherapy, or using the immune system to target cancer cells in various ways, was the hot topic. It is still a hot topic, but not to the level that KRAS is.
“There is going to be a wave of new drugs that attack the major single driver of pancreatic cancer, which is almost always driven by KRAS,” he said.
Scientific lecture also set
In addition to the free public lecture, which will include time for questions and answers, McCormick will deliver a scientific lecture at 3 p.m. in Room 041 of the Avera Health and Science Center on the SDSU campus on “Targeting KRAS and its Direct Effectors.”
Funding for the lectures comes from the Francis Miller Endowment, which was created by Francis J. “Johnny” Miller, a longtime pharmacist and drugstore owner in Redfield and Huron as well as in his hometown of Gettysburg. Assets from his trust became available to the SDSU Foundation after the death of his daughter, Frances Miller Anderson, in 2009.
Miller, who died in 1987, was appreciative of short courses conducted by SDSU because his only training was a 90-day course in Denver during the Great Depression.
