Gynecologic oncologists at the UCLA Health Jonsson Comprehensive Cancer Center (JCCC) are leading groundbreaking research aimed at the clinical challenges they encounter while providing direct patient care through every stage of treatment.
Ritu Salani, MD, MBA, director of the Division of Gynecologic Oncology at the David Geffen School of Medicine at UCLA, said women diagnosed with cervical, ovarian, uterine/endometrial, vaginal and vulvar cancers have access to promising studies and top specialty care.
“We have a very large clinical trial profile which allows us to have access to novel therapies and new treatment strategies for our patients with gynecologic cancers,” Dr. Salani said. “I think it’s important to understand what the treatment landscape is, how it’s shifting, and to be on the cutting-edge of the therapies that are being developed to have an impact on survival outcomes and quality of life.”
Dr. Salani said outcomes tend to be better for women who seek treatment from a gynecologic oncologist. They are trained to not only perform surgery but oversee chemotherapy/systemic therapy and work closely with radiation oncologists. Patients from across the state seek out members of UCLA Health’s six-person team.
Researchers at the UCLA Health JCCC are conducting clinical trials that run the gamut, from treating pre-cancer in the cervix to combination therapy for recurrent ovarian cancer that comes back within six months of treatment.
“At UCLA we are very committed to providing the best care for our patients with gynecologic cancers,” Dr. Memarzadeh said. “We do this by virtue of collaborative, individualized care for patients and collaborative scientific research.”
Dr. Salani, who is also a professor of obstetrics and gynecology, is leading several clinical trials for ovarian and endometrial cancers, including a recurrent ovarian cancer study that combines chemotherapy with a targeted drug designed to make cancer cells sensitive to treatment.
Her area of focus is finding new therapeutics for cervical cancer, including a study for advanced cervical cancer that adds immunotherapy to radiation.
Dr. Salani is in the early stages of developing a study of new immunotherapy combinations in patients who have experienced a recurrence of cervical cancer after previously undergoing immunotherapy. She said their treatment options are limited and the hope is to find a strategy to re-challenge the immune system to fight the cancer.
“Immune therapy has become the mainstay of treatment for patients with advanced cervical cancer,” Dr. Salani said. “I think providing patients with another avenue of treatment is really important.”
Dr. Salani said she’s very optimistic about researchers making more discoveries to benefit the roughly 100,000 women who are diagnosed with a gynecologic cancer each year.
“One of the really exciting things is companies are interested in drug development and disease states that are not as common, including all gynecologic malignancies,” she said. “We’re seeing a dedicated effort into the care of women with gynecologic cancers. These therapies and efforts have resulted in a lot of new treatments for patients that are now standard.”
Dr. Memarzadeh, director of the Gynecologic Oncology (G.O.) Discovery Laboratory, and a member of JCCC, is studying the causes of ovarian and endometrial cancers, including investigating how normal cells may be acting as precursors for cancer. The lab is also working to overcome treatment resistance, where cancer cells stop responding to treatment.
Dr. Memarzadeh, who is also a gynecologic cancer surgeon and professor of obstetrics and gynecology, said aggressive, high-grade forms of ovarian and uterine cancer often relapse despite surgery and chemotherapy. Once the cancer recurs, it’s often more resistant.
“In the laboratory, what we are investigating using patient samples, is: Why does the cancer relapse? One hypothesis is, could there be repopulating of tumor cells that are resistant to standard treatment and could they have characteristics that allow them to evade the patient’s own immune system.”
Dr. Memarzadeh said the lab is tackling this question from multiple angles, including seeking to understand what is unique about the resistant cells and how they can be exploited as targets for effective treatment.
Researchers are also studying immunotherapy, which works for only about 1 in 10 ovarian cancer patients.
“Ovarian cancers often escape currently available modes of immune therapy,” Dr. Memarzadeh said. “We’re thinking of new and different ways, either engineered cells or activated immune cells that can be infused into the patient.”
Dr. Memarzadeh said she’s hopeful that clinical trials originating from her research in collaboration with colleagues at UCLA will be ready in a couple of years.
“The reality is outcomes of patients with ovarian cancer haven’t really changed significantly over the last several decades,” she said. “We need to do basic research that can then be translated to evidence-based clinical trials that can help the lives of these patients.”
Dr. Lai, an assistant professor of gynecologic oncology, is the co-principal investigator for a clinical trial studying immunotherapy for the treatment of cervical dysplasia, a pre-cancer caused by the human papillomavirus (HPV) that can be detected through a Pap smear.
“This is an interesting study because immunotherapy is used in advanced cervical cancer right now,” Dr. Lai said. “It’s relatively low toxicity and has had pretty promising results. We’re looking to assess the efficacy in pre-cancers of the cervix.”
HPV is a common virus and high-risk strains that persist can eventually cause cancer. Currently, the abnormal, pre-cancerous cells must be removed during a surgical procedure, which must be repeated with every recurrence.
“We don’t necessarily have a great treatment for HPV so we end up treating the sequela of HPV, which in some women requires multiple surgeries,” Dr. Lai said. “For younger women of childbearing age, having repeated excisions increases the risk of pregnancy-related complications.”
If the trial is successful, Dr. Lai said, she’s hopeful that immunotherapy could treat vaginal and vulvar pre-cancers caused by HPV.
Dr. Lai is also the principal investigator of the VIRGO Project, a study using artificial intelligence to fine-tune treatment for patients with ovarian cancer, in order to minimize medication side effects and improve quality of life.
The trial, launching in a few months, will look at medication adherence, adverse events, hospitalizations and survival rates. Patients will use a mobile app to record their sleep quality, amount of energy and level of contentment.
“One thing about being involved in research, you constantly are looking for ways to better treat patients, whether that’s symptom management or palliative care,” Dr. Lai said. “It kind of forces us to stay up-to-date and really think outside the box to be able to care for patients better.”
Prevention and awareness
In addition to the importance of research, the gynecologic oncologists said awareness and prevention are essential for a group of cancers that may have vague symptoms or be uncomfortable to discuss.
Dr. Salani said some women mistakenly think that Pap smears and HPV screening for cervical cancer can also detect ovarian or uterine cancer. She said it’s important for women to familiarize themselves with the symptoms.
Signs of ovarian cancer include: abdominal bloating, feeling full quickly after eating, pelvic or abdominal pain and changes in bladder function.
For uterine cancer, symptoms may include: irregular periods, postmenopausal bleeding, abnormal vaginal discharge and changes to bladder or bowel habits.
“Many patients have symptoms for an extended period of time before being diagnosed,” Dr. Salani said.
Dr. Memarzadeh said it’s important for girls and women to get vaccinated against HPV and educate themselves about their bodies. Knowing one’s family history is also important because there can be a genetic predisposition for some gynecologic cancers.
“Sometimes there’s reluctance to talk about cancer that involves the female genitals and organs,” she said. “It’s important for us to be advocates for our patients, raise awareness and talk about the signs and symptoms.”
Dr. Lai noted that cervical, vulvar and endometrial cancers can be diagnosed at relatively early stages if patients seek care for symptoms and undergo routine gynecological exams and screenings. She said patients should feel “empowered to seek care when something feels off.”
For women who are diagnosed, the JCCC offers services ranging from genetic counseling to survivorship support.
“The UCLA family is prepared to take care of them,” Dr. Memarzadeh said. “I want them to have hope. We will make sure they get the best treatment available.”
Courtney Perkes is the author of this article.