Ovarian cancer remains difficult to treat, partly because of its ability to manipulate the body’s immune system. These tumors have found ways to send immune system-dampening signals that leave the cancer’s growth unchecked. A team of Stanford undergraduates has proposed a new idea that could change all that.
Cesar Armas ’21, Karen Chen ’22, and Phillip Ipock ’23 received $50,000 from Stanford ChEM-H to bring their idea—jumpstarting the immune’s system offensive mode—closer to reality. The team, which was one of four to participate in the ChEM-H Undergrad Entrepreneurship Program (UEP), has spent over a year developing their idea and learning laboratory skills to independently design and test their therapeutic strategy.
For Armas, Chen, Ipock, and the other participants in UEP, 2020 was a busy year. Six months of developing a scientifically viable idea and solid business plan, under the guidance of academic and industrial mentors, culminated in a December 2020 “pitch night,” when each team presented their plan to a panel of biotech executives who determined which team would receive funding to pursue their project.
Team “Tremsara,” as Armas, Chen, and Ipock are known, impressed the judges with their sophisticated understanding of the clinical need for ovarian cancer treatments and clever idea for taking the brakes off the immune system.
Oliver Dorigo, MD, PhD, Director of Gynecologic Oncology in the Department of Obstetrics and Gynecology at Stanford who has been advising the team, remembers calling into the virtual pitch night immediately after leaving the operating room when he had been caring for an ovarian cancer patient. Still wearing scrubs, he listened to them describe their strategy. “Too many patients die from this disease, and I’m always thinking about how research will translate to better patient care,” said Dorigo. Seeing the project’s potential and the team’s passion, he was excited to see how their idea would evolve toward a real therapeutic.
In addition to $50,000 in research funds, the team also received access to the Medicinal Chemistry Knowledge Center, a state-of-the-art chemical and drug development lab in ChEM-H. The Knowledge Center that houses cutting edge equipment and employs professional scientists to help Stanford researchers turn fundamental discoveries into potential drugs.
Medicinal chemistry is a term that refers to the design and synthesis of therapeutic molecules. But a good medicinal chemist is more than just a molecule constructor. “Medicinal chemistry doesn’t just involve knowing how to make molecules,” explained Mark Smith, PhD, the Head of the Medicinal Chemistry Knowledge Center and Director of the UEP. “It involves understanding unmet medical needs, disease biology, biochemistry, molecular design, pharmacology, intellectual property and anticipating how the molecule could ultimately be formulated into a drug prototype.”
The members of Tremsara have spent over a year becoming medicinal chemists, first by reading up on cancer immunology and then by getting into the lab to build and test their therapeutic prototype.
In their search through papers, the students found that there was a protein found within the tumor environment that seemed to dampen the body’s immune response to cancer. The three students realized that if they could develop a way to get rid of that protein, the immune system would have a better chance of attacking the cancerous cells.
The next step was designing a drug. They ultimately settled on a molecule that would trick a natural cellular pathway into degrading the problem protein, which they hope will kickstart the immune system.
“I have been so impressed by the team’s professionalism, perseverance, and creativity through this whole process,” said Smith.
Armas, Chen, and Ipock spent summer 2021 on campus conducting research full-time. Armas and Ipock focused mainly on refining the design and synthesis of their proposed drug molecule while working in the Medicinal Chemistry Knowledge Center.
“Unlike other research experiences I’ve had, I can’t rely on someone else to have all the answers. We have to be the experts now, and we have to make big decisions that impact the direction of the project. I’ve really enjoyed that freedom,” said Armas.
Chen spent most of the summer in Dorigo’s lab to develop ways of testing their drug prototypes in cells. Since Dorigo regularly treats ovarian cancer patients, the team has been able to use real patient samples to get a better idea of what might be most likely to work in a clinical setting.
“While it’s still early, I’ve been impressed with the data, and I think this is a very promising potential new therapeutic strategy for these patients,” said Dorigo.
Armas and Chen, who are considering pursuing dual MD/PhD degrees in the future, said that their experience seeing how the drug development process works reinforced their career goals. For Ipock, who had planned to major in biology, the experience inspired him to major in chemistry. “Chemistry is central to science and to biology, and I’ve learned that looking at a problem from a molecular perspective can really help you solve a lot of problems in medicine,” said Ipock.
For Chen, who from the start advocated to her teammates about the need for better ovarian cancer, the experience has been empowering. “It’s helped me realize that if I see a problem, I have to go solve it, because maybe no one else has reason to,” said Chen. “I feel more of an obligation to work on drug development in the future because now I know that I’m capable. And if I don’t do it, who will?”