Kidney cancer physician-scientist to lead precision oncology effort at Hollings

As the number of cancer treatments focused on very specific subsets of patients increases, physicians are faced with an array of choices. Some treatments target specific mutations or are available only after a patient has tried other therapies first.

To help physicians within the MUSC Health system and the Hollings Cancer Network – and, eventually, any oncologist in South Carolina – MUSC Hollings Cancer Center has recruited Thai Ho, M.D., Ph.D., to lead the development of the Precision Oncology Program and a precision oncology tumor board. He has been named to the Blatt-Ness Distinguished Endowed Chair in Cancer Research.

As a physician-scientist, Ho has a foot in both aspects of the cancer world. He treats patients with genitourinary cancers, like kidney, bladder, upper tract urothelial and prostate cancer, and he runs a lab where he focuses on researching a mutation in the gene SETD2 that occurs in kidney cancer.

“I found that SETD2 mutations are associated with an increased risk of metastasis, and this has been the crux of my research,” he said. “The gene encodes for protein implicated in DNA repair and regulating the DNA structure inside cells.”

Kidney cancer is among the top 10 cancers diagnosed in Americans. Ho noted that the mutations in kidney cancer are different from mutations such as KRAS or P53 that are found in most other types of cancers, which makes kidney cancer somewhat of an outlier.

“Mutations that occur in these genes that regulate how our DNA blueprints are compacted usually occur in greater than 50% of kidney cancer, so it makes these genes more frequently mutated than the conventional P53 or KRAS genes,” Ho said. “This is sort of unusual in that this particular cancer is not as driven by KRAS or P53, which are the canonical growth pathways in cancer.”

A further intriguing fact about SETD2: inherited mutations in children can lead to significant developmental delays while spontaneous mutations in adulthood can lead to cancer.

“It’s interesting how one gene can control two different things,” he said. 

"I think the patients like the idea of having a second opinion without having to physically travel to a site that they may not have access to.”

Thai Ho, M.D., Ph.D.

Ho’s interest in the driving genetic forces behind cancer coupled with his experience in individualized medicine make him an ideal fit to lead the growth of precision oncology at Hollings.

Ho said he anticipates that the precision oncology tumor board would be composed of physicians from a variety of subspecialties, all united by an interest in applying genomics for the purposes of identifying clinical trials or treatments for patients, including what’s known as compassionate care, which involves providing a medication that hasn’t yet received FDA-approval when the patient has no other options. This compassionate drug use exception is a possibility when doctors believe that a drug currently in clinical trials could improve a patient’s quality of life or extend life.

The board would serve as a resource for oncologists looking for options for their patients.

“The patient may not physically be able to travel, but they could still be receiving care that's directed by specialists and physicians who are comfortable interpreting next-generation sequencing,” Ho said. The patient’s oncologist would present all the relevant information to the board, and the board would come to a consensus or majority opinion about which treatment to recommend. “I think the patients like the idea of having a second opinion without having to physically travel to a site that they may not have access to.”

Ho said he’s also interested in expanding genetic screening to be more inclusive.

“The challenge with all our cancer genomes and databases is that these are often from a Caucasian population, and that's not reflective of the diversity that we have in America or South Carolina,” he said. “Kidney cancer also strikes more men than women for unclear reasons. So, there are all sorts of background genetic factors that may influence the development of kidney cancer, and I think this is what makes it very interesting.”

Kidney cancer is also more prevalent in military populations, which led to a Department of Defense grant for Ho’s work. The increased risk in military populations, as with those who work in the oil and petroleum industry, may be due to exposure to certain toxins, Ho said.

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