Genome Analytics Could Boost Precision Medicine for Kidney Cancer

Scientists at City of Hope and the Translational Genomics Research Institute (TGen) are accelerating precision medicine and personalized treatments for kidney cancer using an advanced genome analytics tool.

Nearly 74,000 new cases of kidney cancer will be diagnosed this year, and about 14,800 people will die from the disease, researchers noted. Experts know that patients who have certain genetic mutations are more susceptible to specific drugs, but most doctors are not genetically sequencing each kidney cancer patient’s tumors.

"It's a paradox: We don't use targeted therapy in a targeted fashion," said Sumanta Pal, MD, one of the study's senior authors and co-director of the Kidney Cancer Program at City of Hope. "At City of Hope, we have begun to provide comprehensive genome and exome sequencing for all patients with Stage 4 cancer, regardless of their cancer site."

By genetically profiling the tumors of every single patient, the organization expects to enable patients to receive effective targeted therapies or to enroll people in innovative clinical trials as early as possible so they can fight their disease.

In a study recently published in the Journal of Immunotherapy of Cancer, researchers from City of Hope sent samples of 91 patients’ tumors to TGen’s clinical laboratory so that specimens could be sequenced.

Scientists used a leading genome analysis tool that features tumor-normal whole exome sequencing and tumor whole transcriptome sequencing. These techniques are molecular-level analyses of each patient’s entire protein-coding DNA and RNA.

"The goal was to identify genomic alterations that correlated with therapy response," said Sara Byron, PhD, assistant professor in TGen's Integrated Cancer Genomics Division and co-senior author of the study. "We wanted to use this 'real-world evidence' to explore potential molecular and genomic features associated with response."

The study’s results suggested that mutations in the TERT gene predict that a patient may not be receptive to immune checkpoint inhibitors such as nivolumab or pembrolizumab.

"The hope is to one day identify patients who will benefit from immunotherapy and those who will not. Eventually we may be able to distinguish which patient is better suited for other treatments, like targeted therapy," said Pal.

Kidney cancer treatment regimens involving either targeted therapy or immunotherapy have rapidly increased since 2015, and scientists have not yet found the ideal strategy to sequence regimens for optimal outcomes. In addition, the current method of treatment assessment tends to be subjective and is prone to ingrained bias, researchers said. The organizations are working to develop objective laboratory-based biomarkers for kidney cancer.

Only patients whose genomic profiling was performed prior to systemic treatment were included in the study. Patients received either targeted therapy or immunotherapy, and were divided into those who received no clinical benefit, meaning their disease progressed, or those who received clinical benefit, meaning the disease shrunk or stabilized for more than six months.

Researchers analyzed some 19,396 genes and nucleic sequences to uncover a therapeutic treatment plan that would have best suited each patient based on their specific tumor mutations. The team noted that future studies should conduct research in larger sample sizes, but the group expects that their findings could enhance precision medicine for kidney cancer.

“Stage 4 cancer is often considered incurable, but that doesn't always have to be the case," Pal said. "By sequencing all protein-coding DNA, that is by sequencing the whole exome, we may be able to identify new therapeutic targets, and that's a very exciting prospect."