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Using personalized medicine to target gynecological cancers

Gynecologic cancers, any cancer that starts in a woman’s reproductive organs, impacts more than 100,000 American women every year. While many of these cancers are often treatable when detected early, many are often diagnosed at more advanced stages, when treatments are less likely to work.

But Ritu Salani, MD, the director of gynecologic oncology at the UCLA Health Jonsson Comprehensive Cancer Center, remains optimistic that as research continues to advance the understanding of gynecological cancers, it will lead to improved diagnostic methods, treatment options and outcomes.

In this interview, Dr. Salani, who is also a professor of obstetrics and gynecology in the David Geffen School of Medicine at UCLA, talks about the latest research advances for these cancers and how women can help reduce their risk and help with the early detection of the five main types of gynecologic cancers: cervical, ovarian, uterine, vaginal and vulvar.

First, what are some of the most exciting advances that have really made a difference in this field?

I think the most exciting advances in gynecologic cancers across the board are these new therapeutic targets that are personalized. What that means is we’re testing tumors for specific markers —whether it’s finding a marker on the cancer cells or a mutation within the cancer cells — and then targeting that marker or mutation specifically, to provide better outcomes and hopefully minimize toxicities. And right now, we have these targets for cervical cancer, endometrial cancer and ovarian cancer but we’re continuing to explore other options as well.

What is your specific research focused on?

My main research is focused on cervical cancer and innovative therapeutic approaches tailored to this cancer. While immunotherapy has made an impact in this area, we want to find ways to move that line of treatment to primary diagnosis, where you can actually reduce the chance of recurrence or prevent it altogether.

We also are looking at other novel strategies. We know that once cancers are present in advanced or recurrent settings, they become much more challenging to treat and one therapy is often not enough. So, we are really looking at the tumor profile, whether it’s the mutation or the expression of markers, and trying to understand what we can target and what’s effective. Just because a tumor has an expression of something doesn’t mean it’s actually a driver. Your tumor might express, let’s just say, marker X, but marker X is actually irrelevant. Understanding what’s relevant and meaningful is what I’m hoping to uncover and we do this by looking at different therapies and the cancers’ responses to therapies.

What type of clinical trials does UCLA offer for these cancers?

We have a pretty wide portfolio of clinical trials here at UCLA. To start, there are trials that look at prevention or efforts to understand tumor biology better. And this isn’t necessarily restricted to patients who have cancer – this actually includes patients with benign and normal tissue as well.  Understanding normal, benign and cancer changes, can help us develop future therapies. Any patient who is undergoing surgery has an opportunity to participate in specimen-related research. We also have trials looking at genetic testing and risk-reducing surgery to help understand long-term side effects from these procedures.

Our largest portfolio is focused on treatment clinical trials. We have trials looking at precancerous lesions of the cervix and non-surgical treatment approaches. And then, of course, clinical trials that are addressing cancer therapies. And these can be how do we not only improve outcomes, but how do we also improve quality of life for patients? We also have a number of trials that are looking at novel treatments or combinations and we have these across the cancer types including immunotherapy-related trials. One area of excitement are the antibody drug conjugates, or ADCs, which are making a really exciting impact in the gynecologic cancer space. These are being studied both independently or in combination with chemotherapy.

We also have what we call maintenance therapy trials. We know that certain cancers are high-risk of coming back. We’re looking at strategies to help reduce that risk by administering additional treatment and confirming it is improving outcomes without resulting in unnecessary side effects. 

What can women do to reduce their risk and or help with the early detection of gynecologic cancers?

It’s always important to recognize that there’s screening and there’s early detection for some of these cancers. Pap and HPV testing as well as the HPV vaccine are ways to prevent or catch cervical dysplasia and cervical cancer early. These screening tests can really have a significant impact on one’s livelihood. It’s also important to recognize the Pap test doesn’t pick up all gynecologic cancers. It’s really just for cervical cancer.

For endometrial cancer or uterine cancer, bleeding is a major sign. If you have abnormal bleeding, such as any bleeding after menopause, it warrants further evaluation. If you are experiencing vaginal bleeding, make sure you discuss your symptoms with your doctor.

Ovarian cancer is one of the bigger challenges because there’s not really early signs or symptoms that are telling, but it is a matter of paying attention to your body and understanding that certain symptoms, such as bloating, abdominal pain, or feeling full early, particularly if these symptoms persist, should prompt medical attention. One of the most important things you can do is to know your family history. Even though only about a quarter of patients who have ovarian cancer have a genetic predisposition, it can make a difference and lead to opportunities for earlier monitoring and intervention.

I always say women are very slow to report symptoms and I think it is really important that we advocate for ourselves. If you have symptoms that just don’t feel right, it’s important to talk about it with your doctor because it may lead to an earlier diagnosis and better outcome.