Targeting the Uncommon: Rare Cancers

Article Content

For any patient diagnosed with a rare form of cancer, that cancer is anything but rare. A cancer is classified as rare when it affects fewer than 40,000 people per year. Still, these diseases collectively represent 27% of all cancers and account for 25% of cancer deaths — an impact that often goes overlooked, leaving patients with far too few treatment options and research opportunities.

Despite their cumulative toll, rare cancers often lack effective therapies, research funding and opportunities for clinical trials. But investigators at UC San Diego Moores Cancer Center aim to close this gap.

Tailoring Treatment to Individual Tumors

Rare forms of cancer require treatment approaches that are far from one-size-fits-all. Jason Sicklick, MD, professor of surgery at UC San Diego School of Medicine and co-leader of the Structural and Functional Genomics Research Program at Moores Cancer Center, is leading a transformative clinical trial known as the Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy, or I-PREDICT. This study uses the unique genetic blueprint of each patient’s tumor to craft a truly personalized drug treatment — combining multiple drugs to target several of the tumor’s key genetic drivers at once. It’s precision medicine taken to the next level.

“Most tumors have multiple cancer-causing mutations in them,” explains Sicklick. “One might be the main driver, but if we can identify and address the secondary molecular alterations simultaneously, we can be more effective. The better we can target, the better people do.”

Sicklick has successfully used I-PREDICT’s novel treatment approach for gastrointestinal stromal tumors, his area of clinical focus, as well as applied it to a wider range of both rare and more common cancers. When Teresa McKeown, a breast cancer patient at UC San Diego Health, saw Sicklick in 2016, she learned she was a candidate for the I-PREDICT trial. Today, Teresa is cancer free, a testament to what’s possible when innovation meets individualized care.

“It’s unbelievable to be disease-free when nine years ago, I was on the cusp of hospice care,” says McKeown.

Bringing Innovation to Treat Rare Abdominal Tumors

Andrew Lowy, MD, chief of the Division of Surgical Oncology, is an expert in pancreatic cancer and also specializes in rare abdominal cancers, particularly those of the pancreas and gastrointestinal (GI) tract, including tumors of the appendix. Since joining UC San Diego in 2007, Lowy has led a comprehensive effort to treat cancers of the appendix combining tumor-removing surgery with heated chemotherapy (HIPEC) delivered directly to the abdomen, as well as a laboratory-based research program designed at finding new, more effective therapies.

Lowy and his team recently described the first use of appendix cancer tissue models to test new drugs in the laboratory, a breakthrough that paved the way for the discovery of promising new therapy for appendix cancer. Palbociclib, a drug traditionally used to treat breast cancer, has shown remarkable potential in treating this rare disease.

“This was especially exciting because as an existing drug, it is already FDA approved,” says Lowy. “We already knew its side effect profile and how to give it safely, and we could move quickly into trials.”

Working in collaboration with Shumei Kato, MD, associate professor of medicine and medical oncologist, Lowy enrolled patients on PREDICT, demonstrating Palbociclib as the first truly effective targeted therapy for appendix cancer — and possibly other cancers which share similar genetic mutations.

“To understand the mechanism behind this response could help us broaden the scope of the therapy, applying it to cancers that arise in the pancreas, for instance. But already this marks a significant advancement in our fight against a subset of appendix cancer.”

Patients across the U.S. are even starting to benefit from this bench-to-beside discovery — after publishing results of the study in the Journal of Clinical Oncology, Lowy has heard from other medical centers about patient successes, and insurance companies have even extended coverage for the treatment based on the report.

Saving Lives, Preserving Sight

Nathan Scott, MD, MPP, division chief of ocular oncology, is leading advancements in the treatment of uveal melanoma, a rare and aggressive cancer of the eye. While treatment has steadily advanced with methods like brachytherapy, many patients still face a difficult trade-off: saving the eye, but losing their vision.

“Tumor control within the eye has come a long way,” Scott says. “With radiation therapy we no longer need to remove the eye, but now we have to focus on preserving vision after treatment.”

Up to half of patients receiving radiation experience side effects that can lead to blindness. Scott is now investigating preemptive treatments, such as steroid injections, to mitigate this damage. He’s also spearheading two clinical trials aimed at reducing or even avoiding radiation altogether. One involves a light-activated drug that targets tumors near critical vision structures. Another trial tests medications that shrink tumors before radiation, allowing for lower doses and a better chance of preserving sight.

Beyond preserving vision, Scott’s work could have far-reaching implications. Uveal melanoma frequently metastasizes to the liver, and by studying this spread, his research may reveal why some cancers seek out specific organs.

“Rare cancers hold a unique mechanistic place in science and biology. By studying them, we can learn how cancers leave their primary spot, how they target an organ, or what’s happening in that organ that makes it advantageous for a cancer cell to grow. This knowledge could inform interventions that may help all cancers.”

At Moores Cancer Center, no cancer is too rare to deserve attention — or a cure. Through innovative personalized research like I-PREDICT, repurposing existing therapies for new targets, and refining treatments that improve both survival and quality of life, we are advancing oncology nationally and giving patients with rare cancers bold new options for the future.

Read the rest of the Moores Cancer Center FY25 Annual Report here!