Daphne Haas-Kogan: Tumor Ace

First published June 2003

Daphne Haas-Kogan treats adults and children with life-threatening tumors, sometimes caring for the same patients daily for weeks on end. In what seems a world apart from the intensity of these clinical encounters, she also conducts laboratory searches for clues to the life-and-death mysteries of the cancer cell.

As a teen, she began trying to decide between a career in science and medicine, a dilemma that lasted years. But today, her worlds are merging. Her lab findings are stimulating new ideas for clinical trials, and clues from the outcomes of clinical trials and from patients' tumors are influencing the direction of new lab studies.

"I had the sense it would be easier in the long term if I did either research or clinical work, but I always loved both," she says. Indeed, Haas-Kogan, who has been at UCSF since medical school and who now is an assistant professor of radiation oncology, gives the impression of being unwilling to give up on any of her strong interests -- kids, for instance -- out of any belief that one simply cannot do it all, or do it all at once, for that matter.

She bore three children before she completed training for her current career. In part, she credits her ability to persist to a partnership "as equal as possible" with her husband, Scott Kogan, a physician and assistant professor of laboratory medicine at UCSF, and o people both within and outside UCSF who pitched in well beyond their professional duties to find or provide child care for the growing family.

The daughter of two scientists, Haas-Kogan often accompanied her parents to work and learned how to make herself at home in a laboratory. At 16, she began her first lab job at San Diego's Salk Institute. But as a Harvard undergraduate, she quickly came to enjoy personal relationships she developed with children as a tutor and as a soccer coach for inner-city kids, and as a volunteer reader making rounds with a library cart at Boston Children's Hospital. As a result, she decided to go to medical school, leaning toward a specialty in pediatric oncology. Still, she kept a foot in the lab, taking a year out of medical school to conduct cancer research as a Howard Hughes Medical Institute fellow in J. Michael Bishop's UCSF laboratory.

After Haas-Kogan had her first child -- and worried about the continued emotional wear-and-tear of caring for very sick pediatric patients -- she acted on a friend's suggestion and arranged a rotation in radiation oncology. It was a field, she was told, in which she could see either children or adults, and where opportunities both to do basic science and to translate research discoveries into the clinic were expanding rapidly. The forecast proved true, and after finishing the rotation and working two years at UCSF's Brain Tumor Research Center, she completed a residency in radiation oncology. Thankfully, when she accepted an offer to join the faculty in 1997, there was no need for her to choose between medicine and science; instead she was encouraged to conduct science in addition to practicing medicine.

Disarming gliomas

Haas-Kogan now studies a type of brain tumor called a glioma, one of the most deadly malignancies. While radiation therapy following surgery to remove as much tumor as possible has been the standard glioma treatment for decades, clinicians have had little success in curing the disease. "The treatment is effective, but not effective enough," Haas-Kogan says. "We have known for a long time that making headway in the treatment of glioma is going to be extraordinarily challenging, because for many years we have not made much progress in prolonging patient survival."

Haas-Kogan was struck by how gliomas are innately very resistant to treatment, including standard radiation and experimental chemotherapy. Like other scientists working in radiation oncology, she has gravitated toward examining the genetic determinants governing how cancer cells respond to treatment. Tumors that arise from different tissues tend to have differing susceptibilities to radiation treatment, and in part, these differences can be traced back to the responses of the normal tissues, Haas-Kogan explains. For instance, white blood cells, or lymphocytes, normally die when exposed to radiation, and the cancers these cells give rise to, for example lymphomas, are highly susceptible to radiation and have a high cure rate. On the other hand, normal astrocytes, the cells from which gliomas arise, typically do not die when treated with radiation; instead they stop proliferating.

In a UCSF Comprehensive Cancer Center collaboration with biochemist David Stokoe, Haas-Kogan is investigating the chain reactions of biochemical events within cells, called "signaling cascades," known to contribute to the development of tumors. Some newer drugs, including a few that have shown a promising ability to kill glioma cells in early clinical trials, target these signaling cascades, but little is known about how this targeting triggers the death of glioma cells. Haas-Kogan and her colleagues are investigating the effects of both radiation therapy and experimental drugs on signaling cascades, to better understand the biochemical mechanisms that act within the cells and to get a better sense of how to design new and more effective treatment regimens. Haas-Kogan and Stokoe have found that more than 30 percent of advanced gliomas exhibit abnormalities in one particular signaling cascade, and they have gathered preliminary evidence showing that inhibiting this cascade can make glioma cells more vulnerable to radiation therapy.

In the clinic at the UCSF Medical Center, Haas-Kogan treats adults with brain tumors, and children with any kind of tumor. She is working with clinical colleagues to develop new protocols for treating children who have brain tumors with combinations of promising experimental drugs and radiation.

While the opportunity to relate to children and families that first drove Haas-Kogan toward medicine continues to be rewarding, she now finds laboratory collaborations -- and university friendships -- equally satisfying. When she was still in medical school and pregnant with her first son, Haas-Kogan recalls Karen Smith-McCune (profiled on page 20), who was then an ob-gyn resident, helped deliver the baby. Years later, Haas-Kogan has been able to help Smith-McCune's daughter hone her soccer game: she still coaches local teams, despite the fullness of her days.

"I just really love soccer, and I love hanging out with kids," she explains.

Daphne Haas-Kogan. Photo by Fiona McDougall/OneWorld Communications Inc.

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