Gynecologic Cancers


Gynecologic cancers originate in the female reproductive organs, including the uterus, ovaries, cervix, fallopian tubes, vulva and vagina. More than 80,000 gynecologic cancers are diagnosed in the United States each year, and about half of these cases are endometrial (uterine) cancer, with more than 20,000 cases being ovarian cancer.

Gynecologic cancer is a serious disease, but in the majority of cases it can be treated and cured.

At the OSUCCC – James, our treatment team is dedicated to providing excellent, research-based clinical care for women who have or are at risk for gynecologic cancer. Working closely together, our physicians and researchers are better able to translate scientific advances to innovative patient care.

Gynecologic cancers may be treated by surgical procedures, radiation therapy and/or chemotherapy. At the OSUCCC – James, our gynecologic cancer treatment team includes specially trained medical, surgical and radiation oncologists along with experts in clinical cancer genetics. A board certified gynecologic oncologist functions as each patient's primary care cancer physician during the diagnostic, treatment and follow-up phases of her care.

Research Strengths

  • Examine all molecular aspects of gynecologic cancer cells—genetic, epigenetic, RNA/protein, non-coding RNAs and biochemical—and integrate these features to improve cancer risk stratification and to more effectively direct targeted therapies toward each person’s unique cancer
  • Develop immunotherapeutic approaches that bolster the human immune system’s innate ability to combat gynecologic cancer
  • Devise targeted therapies to prevent or improve the treatments of gynecologic cancers

Grants

Clinical research on promising investigational treatments for gynecologic malignancies at the OSUCCC – James is supported by numerous grants both private and public, but particularly from the National Institutes of Health. Here are a few examples:

The Ohio State University as Network Lead Academic Participating Site for the NCI National Clinical Trials Network (NCTN) (1 U10 CA180850 01) PI: Richard Goldberg, MD, physician-in-chief at the OSUCCC – James Co-PI: David Cohn, MD, director of the Division of Gynecologic Oncology at Ohio State Objectives:

  • Provide infrastructure to support Ohio State’s participation in the scientific and clinical research activities of the NCI's NCTN Program as a Network Lead Academic Participating Site (NLAPS)
  • Use this support to make scientific discoveries about tumor biology, find better treatments and augment quality of life for patients, thus improving outcomes across the spectrum of cancers affecting adults
  • Investigate new therapeutic agents and their toxicities in phase I to II clinical trials
  • Evaluate the efficacy and toxicity of novel combinations based on preclinical data to exploit drug combinations more effectively
  • Develop multi-modal approaches using surgical, immunological and radiotherapeutic measures in optimal combinations
  • Integrate experts in molecular genetics, biochemistry, pharmacology, immunology and biostatistics in the design and execution of therapeutic protocols
  • Improve cancer outcomes through discovery and education of pre- and postdoctoral students, nurses, allied medical personnel and physicians
  • Understand and exploit tumor heterogeneity to exploit the value of targeted therapies
  • Improve management of cancer-related symptoms

Dissecting the Role of Stat3 and Targeting Ovarian Cancer (1 R01 CA176078 01A1) PI: Selvendirian Karuppaiyah, PhD Objectives:

  • Further elucidate mechanisms of STAT3 activation in ovarian cancer and determine how this contributes to drug resistance
  • Use an in vivo orthotopic ovarian cancer model to evaluate whether diarylidenyl piperidone (DAP) compounds can overcome hypoxia-related drug resistance and increased toxicity
  • Advance the understanding of ovarian tumorigenesis and use this knowledge to improve treatment for ovarian cancer patients who develop hypoxia-mediated chemotherapy resistance

Examples of Clinical Trials for Gynecologic Cancers

Recurrent Cervical:

  • OSU-17059 (LION) – “A Phase 2 Study to Evaluate the Safety, Tolerability and Efficacy of Cell Transfer Therapy Using Autologous Tumor Infiltrating Lymphocytes (LN-145) followed by IL-2 in Patients with Recurrent and/or Metastatic Cervical Carcinoma.”

Upfront Ovarian:

  • OSU-17036 (GOG-3015) - “A Phase III, Multicenter, Randomized, Study Of Atezolizumab Versus Placebo Administered In Combination With Paclitaxel, Carboplatin, And Bevacizumab To Patients With Newly-Diagnosed Stage III Or Stage IV Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer”

Recurrent Ovarian:

  • OSU-15186 (IMGN853-0402) – “A Phase Ib Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination with Bevacizumab, Carboplatin or Pegylated Liposomal Doxorubicin in Adults with Folate Receptor Alpha Positive Advanced”
  • OSU-15273 (Dr. Backes IIT) – “Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer”

Endometrial:

  • OSU-15273 (Dr. Backes IIT) – “Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer”
  • A Phase I Dose Escalation and Cohort Expansion Study of TSR-042, an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors

Advanced Solid Tumor:

  • OSU-17124 – “An Open Label, Phase 1 Study of SC-004 in Subjects with Advanced Solid Cancers”
  • OSU-17185 – “A Phase 1 Trial of the Combination of the Heat Shock Protein-90 (HSP90)inhibitor Onalespib (AT13387) and the Cyclin-Dependent Kinase (CDK) inhibitor AT7519M in patients with Advanced Solid Tumors”
  • OSU-17180 – “A Phase 1, Open-Label, Multiple Ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion to Second-Line Cervical”

Examples of Recent Clinical Research Accomplishments

Pelotonia ‘Idea Grant’ Supports Study of Drug Resistance in Ovarian Cancer. OSUCCC – James researchers received an “Idea Grant” supported by Pelotonia—an annual grassroots bicycle tour that raises millions of dollars for cancer research at Ohio State—to study ways of reversing drug resistance in patients with ovarian cancer.  Chemotherapy kills cancer cells by damaging their DNA so badly the cells can’t repair it. Nonetheless, ovarian cancer recurs in up to 80 percent of patients after treatment with chemotherapy. But these researchers have found that a protein called histone deacetylase 10 (HDAC10) is part of a DNA repair system in cells. They believe this system allows some ovarian cancer cells to survive the damage inflicted by the platinum-based chemotherapy used to treat the disease. This grant will enable them to examine whether drugs called HDAC inhibitors will knock out the HDAC10-powered DNA repair system and make drug-resistant ovarian cancers respond once again to platinum-based chemotherapy. If successful, the project will lay the groundwork for a new treatment strategy that might prolong the lives and reduce the suffering of women with ovarian cancer. Grant awardees are Jeffrey Parvin, MD, PhD, and David Cohn, MD.

Statewide Screening Launched by Ohio State Has Lifesaving Potential. The OSUCCC – OPTEC (Ohio Prevention and Treatment of Endometrial Cancer) is a statewide initiative to help identify women with endometrial cancer who may be at risk for other types of cancers due to their genetic makeup, and to help match women with endometrial cancer to the best treatment options for their particular cancer.

Some endometrial cancer results from an inherited condition called Lynch syndrome. While Lynch syndrome is rare — only about 5 in 100 people with endometrial cancer have Lynch syndrome — it greatly increases the chance of developing many other types of cancer.

Study Shows Benefit of 3-Drug Regimen in Treating Recurrent Ovarian Cancer. A phase II study led by researchers at the OSUCCC – James found that a biweekly regimen involving the drugs gemcitabine, carboplatin and bevacizumab was effective for treating patients with platinum-sensitive recurrent ovarian, peritoneal or tubal cancer. The study, which involved 45 patients and was published in the journal Gynecologic Oncology, found that the three-drug regimen, administered at specific intervals, showed an improved response rate and progression-free survival over outcomes previously reported for patients receiving just a gemcitabine/carboplatin combination. The researchers contend that the three-drug combination should be further evaluated. Larry Copeland, MD, was senior author for the study.

Examples of Translational Research Accomplishments

Novel Agent Could Boost Treatment for Endometrial Cancer. An experimental agent designed by researchers at the OSUCCC – James decreased high levels of a protein that is overexpressed in endometrial (uterine) cancer, and the scientists believe the agent could serve as an adjunct targeted therapy for patients with this disease. Reporting in the journal Gynecologic Oncology, the investigators stated that treatment with HO-3867, a novel agent that inhibits the STAT3 protein, decreased the high levels of STAT3 Ser727 in endometrial cancer cells by inducing cell cycle arrest and apoptosis, or natural cell death. The preclinical study involved cell lines, human tumor samples and xenograft mice. Selvendiran Karuppaiyah, PhD, was corresponding author.

Study Reveals Useful Tool in Characterizing Endometrial Cancer. The National Cancer Institute’s Cancer Genome Atlas described DNA polymerase ɛ (POLE)-mutant tumors as a molecular subtype of endometrial (uterine) cancer with improved progression-free survival. A study led by OSUCCC – James researchers expanded on the Genome Atlas investigation and found that POLE mutations can be a useful tool in determining whether endometrial cancer is a result of sporadic or inherited predisposition to the disease. Paul Goodfellow, PhD, was corresponding author for the study, which was published in the journal Cancer (epub ahead of print).

MMR Protein Expression Study in Endometrial Cancer Finds Biological Associations. In a translational research study of mismatch repair (MMR) protein expression in 1,049 patients with endometrial (uterine) cancer, OSUCCC – James investigators sought to identify relationships among cancer outcome, weight (BMI) and other factors. They found that BMI showed statistically significant associations with MMR expression, tumor grade and stage among the study participants, and that obesity correlates with lower grade and stage endometrial cancer. A link between BMI and maintenance of the MMR system was not supported by the data. The study was published in the journal Gynecologic Oncology.  Adrian A. Suarez, MD, was corresponding author.

HO-3867, a Safe STAT Inhibitor, is Selectively Cytotoxic to Ovarian Cancer. A preclinical study led by OSUCCC – James researchers and published in the journal Cancer Research offered proof-of-concept for an agent called HO-3867 as a selective STAT3 inhibitor to treat ovarian cancer and other solid tumors where STAT3 is widely upregulated. In their study abstract, the researchers state that STAT3 is well corroborated preclinically as a cancer therapeutic target, but they note that translational strategies for its blockade by small molecule inhibitors has been elusive. In this study, they reported the development of a class of bifunctional STAT3 inhibitors, based on conjugation of a diarylidenyl-piperidone (DAP) backbone to an N-hydroxypyrroline (-NOH) group, that exhibits minimal toxicity against normal cells and good oral bioavailability. Selvendiran Karuppaiyah, PhD, was corresponding author.

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