PROVIDENCE – It is a difficult topic to talk about. Ovarian cancer is a highly lethal gynecologic cancer, one that is frequently diagnosed at a late stage after the cancer has already spread. As a result, patients inevitably become resistant to chemotherapy upon disease recurrence.

There is an urgent need to understand factors that predict chemotherapy response and clinical outcomes in order to better tailor treatment approaches and uncover opportunities for novel treatments, according to researchers.

A recently published research study in Frontiers in Oncology, conducted by Dr. Jennifer Ribeiro and her team, sought to define immune signatures in patients with short- versus long-term to cancer progression.

Ribeiro, who works with the Program in Women’s Oncology and the Molecular Therapeutics Laboratory at Women & Infants Hospital, examined the progression of ovarian cancer in patients with increased levels of two specific immune factors, called LAG-3 and ICOS.

These results of the research study were validated in a publicly available database of ovarian tumors with The Cancer Genome Atlas, which showed that patients with higher levels of these two factors lived longer following their cancer diagnosis.

Here is the ConvergenceRI interview with Ribeiro, who also serves as an assistant professor of Obstetrics and Gynecology at The Warren Alpert Medical School of Brown University, talking about the importance of the findings of her team’s research study, an example of the clinical academic research engine at work in Rhode Island.

ConvergenceRI: How much collaboration is ongoing in the field of immunotherapy here in Rhode Island?
RIBEIRO: There are several groups focusing on oncology clinical trials within the Brown University and hospital systems. These include the Brown University Oncology Research Group, the Lifespan Cancer Institute, as well as The Women and Infants Hospital Program in Women’s Oncology. Women and Infants is a leading enroller for gynecologic oncology clinical trials nationwide, which includes immunotherapy clinical trials.

The Cancer Center at Brown University, led by Dr. Wafik El-Deiry, provides a platform for collaboration in clinical and translational cancer research through bringing together clinicians and researchers from the three institutes for regular meetings and seminars.

The director of The Program in Women’s Oncology at Women and Infants, Dr. Paul DiSilvestro, is highly committed to the growth of both clinical and translational research that will eventually benefit all women with ovarian cancer. We have a dedicated team of clinical researchers and collaborations with other departments, such as the Department of Pathology, that help us procure the bio-specimens we need to perform our translational research.

Our department has also created a Gynecologic Tissue Bank in which serum, plasma, urine, and tissue are collected by our clinical research team from consenting patients. It is hoped that this bio-specimen bank can eventually be utilized as a valuable community resource for cancer researchers across the state.

ConvergenceRI: Have you had any conversations with Dr. Annie De Groot and her team at EpiVax, to explore the potential use of the firm’s immuno-informatics program related to developing an in silica approach to identifying solid tumor subtypes related to ovarian cancer and the potenttial for targeted therapies?
RIBEIRO: I have not, but I am always interested in developing new connections with biotech.

ConvergenceRI: Is there any indication that you have found with ovarian cancer and endocrine disruption as a major factor for the prevalence of the disease? In particular, are there particular endocrine disruptors that have been identified as having a potential causal relationship with ovarian cancer?
RIBEIRO: Endocrine disruption does not appear to be a major factor in the prevalence of the disease, but some studies done in the lab with ovarian cancer cell lines suggest it could have a tumor- promoting role. However, one must be cautious when translating these findings to humans, as there is no strong population level evidence that endocrine disruptors increase the prevalence of ovarian cancer. Most studies have focused on the endocrine disruptor Bisphenol A [BPA], as it is the most common endocrine disruptor found in many products.

ConvergenceRI: What kinds of research funding would you like to see invested here in Rhode Island to further your ongoing work?
RIBEIRO: I am very interested in obtaining funding to perform extensive analyses of our human bio-specimens available through our Gynecologic Tissue Bank. These specimens, which are graciously donated by our patients, are invaluable in learning more about this disease.

We are specifically interested in understanding how chemotherapy affects the immune landscape of ovarian tumors, so that we can gain insight into how we can best target the immune response following chemotherapy. This is particularly important for ovarian cancer, because patients always receive chemotherapy prior to any targeted treatment like immunotherapy.

Chemotherapy works very well for ovarian cancer patients when they initially receive it, and it is not until later that resistance develops. Therefore, it is important for us to understand the ways in which chemotherapy and immunotherapy can intersect to work synergistically.

ConvergenceRI: How prevalent is ovarian cancer in Rhode Island, in terms of cancer registry data?
RIBEIRO: At Women and Infants, we get about 70-80 ovarian cancer cases a year, which includes all subtypes of the disease. We are focused on studying the most common subtype, which is high-grade serous ovarian cancer, and accounts for about two-thirds of all cases.

ConvergenceRI: In terms of clinical care options for women with ovarian cancer, what are the current treatment options?
RIBEIRO: Following diagnosis, patients will either have a primary debulking surgery followed by chemotherapy, or receive chemotherapy for several cycles and then surgery.

The standard-of-care chemotherapy regimen for ovarian cancer is a combination of two agents – carboplatin and paclitaxel, and this generally works very well at first. Patients often also receive targeted agents as maintenance therapy. One of them, bevacizumab, is an anti-angiogenic agent that targets the tumor’s blood supply. In addition, PARP inhibitors are approved for patients with hereditary ovarian cancer (mutations in BRCA genes). Many of the patients at WIH are enrolled on clinical trials, so they may receive other treatments or combinations, including immunotherapy, in addition to standard of care chemotherapy.

ConvergenceRI: Are there ongoing peer support networks for women with ovarian cancer in Rhode Island?
RIBEIRO: We have a great relationship with the Rhode Island Ovarian Cancer Alliance. This organization was founded by the family of Jessica Morris, who was a patient in our program. The R.I. Ovarian Cancer Alliance helps to fund research, education and support for patients and their families.

Most recently they have been helping to support some of our patients by providing meals to them on a monthly basis. Our program is also very active with the ovarian cancer walk that they host for ovarian cancer awareness month in September. In addition to this support network, patients frequently get involved with The National Ovarian Cancer Coalition.

Our program also offers support groups that our social workers facilitate weekly, which are very popular with our patients.

ConvergenceRI: What questions haven’t I asked, should I have asked, that you would like to talk about?
RIBEIRO: I would just like to comment on the valuable collaboration we developed with Cofactor Genomics to conduct this study. It is critical to develop these kinds of collaborative efforts between academic- and hospital-based researchers with biotech companies to further scientific research. Their ImmunoPrism® platform has the ability to identify multidimensional biomarkers of disease and response to therapies, and we were able to demonstrate in our study a proof-of-principle that an immune signature is related to improved outcomes in ovarian cancer.

ConvergenceRI: One more question: have you encountered or identified any significant racial disparities in your work on ovarian cancer, in terms of diagnosis or treatment?
RIBEIRO: I’ll start off by saying that as a Ph.D. researcher who spends much of my time in the lab, I probably have had less exposure to these specific disparities than a clinician would.

However, we all know these disparities exist. Disparities in early detection that are common for other cancers, such as breast cancer, may be less of an issue, because a majority of ovarian cancer patients are already diagnosed at a late stage. However, economic and racial disparities are definitely involved because many of the risk factors for all cancers are affected by access to proper healthcare.

Fortunately, there seems to be an effort to begin to address some of these disparities in cancer care with funding provided through foundation research grants, such as those from the American Cancer Society and American Association for Cancer Research.

As a health care organization, Care New England is also taking this very seriously, and in fact just held their inaugural Diversity, Equality, and Inclusion Summit to address some of these issues.