December 19, 2018

A Committed Life

For as long as she can remember, Dr. Beth Karlan has been driven to answer one elusive question: what is the difference between a normal cell and a cancerous cell? While the question is common among medical researchers, Karlan’s progress in discovering at least a partial answer has been both heartening and a continuing stimulus to continue the search.

As the director of the Gilda Radner Ovarian Cancer Program at Cedars-Sinai Medical Center, Karlan is heavily involved in both biological research and clinical care. The author of more than 100 research articles, abstracts, book chapters and reviews, Karlan began conducting ovarian cancer research at Cedars in 1987. By the time she was 34, in 1991, she had already been named as the director of the new Radner Program, named for comedienne Gilda Radner, who died of ovarian cancer and who was treated for the disease at Cedars. In addition, Karlan is also director of Cedars’ Division of Gynecologic Oncology and associate professor in the Department of Obstetrics and Gynecology at the UCLA School of Medicine.

Ovarian cancer kills more women than all other gynecologic cancers combined, and the five-year survival rate has remained approximately 30 percent for more than 30 years — this despite major advances in surgical and chemotherapeutic techniques. Only one in four cases of ovarian cancer is diagnosed early enough to offer a good chance at being cured. Because the disease usually has no symptoms until it has metastasized throughout the abdomen, early diagnosis has been tough to achieve.

“We began the program with the hopes of finding better ways to diagnose this cancer at an earlier stage and to improve the chances for survival,” Karlan said. To that end, the program conducts laboratory research, clinical trials, educational symposia for the public and medical communities, screenings for women at increased risk due to family histories of cancer, and cutting-edge cancer care for patients. Although the program’s focus is not on the “Jewish link” to ovarian cancer, Karlan and her colleagues, including researchers at the University of Toronto, are involved in a project to try to determine just how often a particular gene — the BRCA1 gene — is abnormal in women of Ashkenazi Jewish descent who have already developed ovarian cancer. The carrier frequency of both the BRCA1 and BRCA2 gene is 10 times greater among Ashkenazi women than in the general population, Karlan said. This means that 2.5 percent of Jewish women carry a mutation of either gene, as opposed to a likelihood of only .25 percent in the general population. This does not mean that every woman who has the abnormal gene will develop ovarian cancer. “You can have the mutation but not the disease,” Karlan explained, “because the gene has what we call 91 incomplete penetrance. In other diseases, such as Tay-Sachs, the likelihood of getting the disease once the mutation is present is nearly 100 percent.”

There are, in fact, entire textbooks and medical conferences centered on the issue of “Jewish genetic diseases.” “The fact that Jews have remained a relatively confined segment of the population has allowed certain recessive genes to become expressed, such as the cancer genes,” said Karlan, who graduated magna cum laude from Harvard-Radcliffe College and earned her medical degree from Harvard Medical School. In cystic fibrosis, Karlan noted, one of the most common mutations of the gene responsible for the disease is frequently found among Ashkenazi Jews, while other mutations of the cystic fibrosis gene are found in the general population. Gaucher’s disease and APC, a form of colon cancer, also tend to strike Jews with a frequency out of proportion to their numbers. (Karlan noted that the issue of “Jewish genetic diseases” is extremely touchy to many in the Jewish community, who fear that any discussion of such a phenomenon can become fodder for anti-Semites making claims of Jewish genetic inferiority.)

Currently, Dr. Karlan is focusing her research on understanding the genetic alterations that define the pattern of growth and biology of ovarian cancer. Her laboratory has been performing pre-clinical studies on p53 gene therapy. P53 is a tumor suppresser gene, which is the most frequently altered gene involved in all human cancers. “We are actively enrolling women with refractory ovarian cancer to participate in a p53 gene therapy clinical trial at the same time that we are studying the effectiveness of this therapy in mice,” Karlan said.

Efforts to identify ways to reduce the risk of developing ovarian cancer remain at the forefront for Dr. Karlan and her colleagues. Much is already known. For example, women’s birth control and reproductive patterns clearly have an impact — but it’s less clear how. Dr. Karlan noted that studies have shown that birth control pills taken over a number of years before menopause significantly reduces the risk of developing ovarian and uterine cancers. “It’s a linear relationship,” Karlan said. “Each year a woman takes the pill, it further reduces her risk.” However, multiple pregnancies also reduce the risk of ovarian cancer, as well as bilateral tubal ligation, which reduces the ovarian cancer risk by two-thirds.

Karlan’s work at Cedars is only slightly more consuming than her commitments while not wearing a white lab coat. Married to Dr. Scott Karlan, a general surgeon at Cedars, Karlan is also a mother committed to spending time with her son, Matthew, and daughter, Jocelyn, going to little league games, rollerblading by the beach, planning her son’s bar mitzvah, and “spending time as a family.” Her day begins at 5 a.m., when she works out at home before packing lunches for her kids and signing notes for the backpacks. “It’s the only time I get a little peace to myself,” she said. “I use that time to process what needs to get done that day.”

Karlan, who was recently named “Mother of the Year” by Cedars-Sinai Medical Center’s Helping Hand of Los Angeles, also lectures at numerous professional meetings and has been a visiting professor at the Mayo Clinic, Johns Hopkins University, the MD Anderson Cancer Institute, Stanford and UCLA. “I pack in a lot of frequent flier miles, but can use them to enjoy vacations with my family,” Karlan said. In fact, last January Karlan, who was invited to speak at an international cancer symposium in Tel Aviv, took her husband, children and mother (who had never been to Israel) along for the trip.

Karlan would love to try to expand the number of scientists focusing on ovarian cancer at Cedars, “so that we can advance the field more quickly and reach out to more people. If we had even half the amount of money for ovarian cancer as we have for breast cancer, we could make much greater forward strides,” she said. But an even bigger goal is to enjoy all aspects of her life: “I want to be there for my kids, for my husband, and still maintain the level of excellence professionally that I have come t o expect from myself.”

And, one day, perhaps, to develop a cure for ovarian cancer — a silent and deadly killer.