Skip to content

Gene-sequencing rare tumors – and what it means for cancer research and treatment

Sequencing the genes of cancer patients' tumors has the potential to surmount frustrating problems for those who work with rare cancers. Doctors who see patients with rare tumors are often unsure of which treatments will work. And, with few patients available, researchers are unable to assemble enough subjects to compare different therapies in gold-standard randomized clinical trials. But thanks to gene sequencing, that is about to change.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time

That's the take-away from a fascinating conversation about the implications of personalized tumor-gene sequencing that I had recently with two Stanford cancer experts. Cancer researcher Julien Sage, PhD, is the senior author of a recent scientific paper describing sequencing of a pediatric tumor that affects only one in every 5 million people. Alejandro Sweet-Cordero, MD, an oncologist who treats children with cancer at Lucile Packard Children's Hospital Stanford, is leading one of Stanford’s several efforts to develop an efficient system for sequencing individual patients’ tumors.

In their paper, Sage's team (led by medical student Lei Xu) analyzed the DNA and RNA of one child’s unusual liver tumor, a fibrolamellar hepatocellular carcinoma. The cause of this form of cancer has never been found. Curious about what genes drove the tumor's proliferation, the scientists identified two genes that were likely culprits, both of which promoted cancer in petri dishes of cultured cells. One of the genes, encoding the enzyme protein kinase A, is a possible target for future cancer therapies.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time. Sweet-Cordero is working to develop an efficient system for getting both the mechanics of sequencing and the labor-intensive analysis of the resulting genetic data completed in a few weeks, instead of the two to three months now required. "We're trying to use this kind of technology  to really help patients," Sage said. "If you're dealing with a disease that may kill the patient very fast, you want to act on it as soon as possible."

In addition to giving doctors clues about which chemotherapy drugs to try, gene sequencing gives them a new way to study tumors.

"What’s really important is that, instead of categorizing tumors based on how they look under a microscope, we’ll be able to categorize them based on their gene-mutation profile," Sweet-Cordero said. Rather than setting up clinical trials based on a tumor’s histology, as doctors have done in the past, scientists will group patients for treatment trials on the basis of similar mutations in their tumors. "In my mind, as a clinical oncologist, this is the most transformative aspect of this technology," he said. This is especially true for patients with rare tumors who might not otherwise benefit from clinical trials at all.

And for childhood cancers, knowing a tumor's gene mutations could also help doctors avoid giving higher doses of toxic chemotherapy drugs than are truly needed.

"The way we've been successful in pediatric oncology is by being extremely aggressive," Sweet-Cordero said. Oncologists take advantage of children's natural resilience by giving extremely strong chemotherapy regimens, which beat back cancer but can also have damaging long-term side effects. "We end up over-treating significant groups of patients who could survive with less aggressive therapy," Sweet-Cordero said. "If we can use genetic information to back off on really toxic therapies, we'll have fewer pediatric cancer survivors with significant impairments."

Meanwhile, Stanford cancer researchers are also tackling a related problem: the fact that not all malignant cells within a tumor may have the same genetic mutations, and they may not all be vulnerable to the same cancer drugs. Next month, the Stanford Cancer Institute is sponsoring a scientific symposium on the concept, known as tumor heterogeneity, and how it will affect the future of personalized cancer treatments.

Sage's research was supported by the Lucile Packard Foundation for Children’s Health, Stanford NIH-NCATS-CTSA UL1 TR001085 and Child Health Research Institute of Stanford University. Sage and Sweet-Cordero are both members of the Stanford Cancer Institute, and the National Cancer Institute-designated Cancer Center.

Previously: Smoking gun or hit-and-run? How oncogenes make good cells go bad, Stanford researchers identify genes that cause disfiguring jaw tumor and Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers

Popular posts