Molecular Alterations of Gliomas: A Former Harold Amos Scholar Researches Lethal Brain Tumors

    • September 12, 2013

The problem. Each year more than 35,000 Americans learn they have a brain tumor. Treatment depends on the tumor type and makeup—the more accurate and specific the identification, the more promising the treatment. That’s where the pathologist comes in.

“The way we classify these tumors—gliomas—we look under a microscope, and we say it looks like this or it looks like that. I do that every day,” says Kenneth D. Aldape, professor and chair of the pathology department at the University of Texas MD Anderson Cancer Center in Houston.

“But,” he adds, “even in experienced hands it turns out to be a very crude way of categorizing cancer.” Crude because cancer is a function of molecular genetic alterations, and cancers that look the same under the microscope can be very different molecularly, he explains.

“It’s the molecular stuff that really determines tumor aggressiveness and responsiveness [to therapy]. You need to understand the molecular stuff and try to subcategorize these gliomas based on molecular alterations if you are going to have a chance of treating them successfully.”

Gliomas are the most common and lethal of tumors originating in the brain (as opposed to metastasizing from another part of the body). Deepening medicine’s understanding of their molecular subsets in order to develop more individualized, and thus more effective, therapies has been the chief focus of Kenneth Aldape’s career.

“Using molecular alterations to help classify tumors is just an extension of what pathologists are supposed to do, which is to provide an accurate classification of diseases of the body,” says the physician scientist, an alumnus of RWJF’s Harold Amos Medical Faculty Development Program. (See the Program Results Report for more information.)

The start. Kenneth Aldape came to his line of work if not genetically then certainly through a strong familial influence. His father, Hector Aldape, is a pathologist who shared his profession—literally—with his school-age son:

It was sort of funny. On the weekends he would take me into work. We would do autopsies together. It was a little strange—a kid doing autopsies. That sort of got me into the field, I would say.

The elder Aldape is a native of Mexico and earned his medical degree there before coming north for his residency. He met his wife, a nurse working in the Spokane, Wash., hospital at which he trained.

It’s worth noting that the Aldape family boasts yet another pathologist—Kenneth’s brother, Mark, who practices in Portland, Ore. “I think three pathologists in a five-person family must be close to a record,” observes Kenneth Aldape.

Kenneth grew up in Seattle and completed his undergraduate work at Stanford University in 1986. He laughs when asked if he was always a good student. “No. It took me six years to get through college. I was sort of in and out a bit, trying to find myself.” Part of that process, he says, was wrestling with what he wanted to do next—get a PhD or an MD.

He decided on the latter, earning a medical degree in 1991 from the University of California, San Francisco. He remained at UCSF for his residency and fellowships in neuro-oncology and neuropathology and in 1995 joined the medical school faculty. Six years later he moved to the MD Anderson Cancer Center.

The RWJF connection. While an assistant professor at UCSF, Aldape successfully applied to the Harold Amos program and used his RWJF stipend (ID#s 33349 and 38555) to research the molecular genetics of gliomas.

Among the published papers stemming from his RWJF-supported work was a 2006 article in the journal Cancer Cell describing a classification scheme for gliomas based on molecular alterations. (Abstract online)

“That actually has held up as a very influential paper in the field, if I can toot my own horn a little bit,” says Aldape. “The terms that were established in that paper are still being used today.” The Cancer Genome Atlas, a government-supported research project to improve cancer care, used a variant of the classification, he adds.

Aldape’s investigation of brain tumors has continued full tilt since that article, as evidenced by his lengthy list of research grants and publications. The Amos program, he says, was critical to getting the ball rolling. Or, as he puts it, “The way it works is it takes money to make money:”

Researchers live by grants, right? They write grants to NIH; they write grants to foundations. The people who review these grants look to see what you’ve done because that, in theory, is a predictor of what you can do in the future. So that’s why it takes money to make money. Because you need money to generate the preliminary data to convince people that you’re worth funding in the future. That’s what the Robert Wood Johnson Foundation did—provided that initial seed money.

The move to Texas. In 2001—in his third year of the four-year Amos program—Aldape moved from UCSF to MD Anderson. The Texas institution, he says, offered a greater opportunity to do the kind of research he was intent on doing: translational research, which can have direct clinical implications, rather than basic or pure research.

Today at MD Anderson, Aldape holds an endowed professorship in tumor genetics and since 2012 has been chair of the pathology department. This latter step, Aldape says, has broadened his interest to molecular alterations in—and personalized therapy for—all solid tumors, not just brain tumors.

The titles of most of Aldape’s research projects and publications are technical, almost indecipherable by laypersons, but one entry on his curriculum vitae is plain enough: he is a triathlete. Asked about this outside-the-lab part of his life, he demurs, saying, “I’m happy if I can just finish” a race.

On another personal note, Aldape is married to Herminia Palacio, MD, MPH, for 10 years executive director of Harris County Public Health and Environmental Services, the public health department for the Houston metro area. She left that position in May 2013 to join RWJF as a senior program officer.

Like her husband, Palacio was at one time on the UCSF faculty and an Amos scholar, entering the program three years before he did.

RWJF perspective. The Harold Amos Medical Faculty Development Program is a four-year postdoctoral fellowship launched by RWJF in 1983. Its purpose is to increase the number of faculty from minority and other historically disadvantaged backgrounds who achieve senior rank in academic medicine and dentistry.

The program supports one of RWJF’s major objectives: to increase diversification of the medical and dental professions and, as a consequence, improve the health care received by the nation’s underserved populations.

Of Amos program scholars, RWJF Senior Program Officer David M. Krol, MD, MPH, says:

Ultimately, we would like to see these individuals from historically disadvantaged backgrounds becoming full professors at prestigious institutions, putting out important, valuable work, looking at a variety of different issues—including how to decrease the disparities between rich and poor, majority and minority—while climbing the academic ladder.

Kenneth Aldape is one of more than 180 Amos program alumni in academic medicine today. His career and research exemplify the academic achievement and professional contributions that the program was designed to stimulate.

“The measure of the success of the program is the success of the individuals” who participate in it, says Krol.

Kenneth D. Aldape, MD

Kenneth D. Aldape, MD
Harold Amos Medical Faculty Development Program

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Understanding the molecular profile of #gliomas, lethal brain tumors, is key to treating them successfully