Ovarian cancer is the most lethal malignancy in gynecologic cancers. Although it is the 11^th most common cancer in women, this cancer remains the 5^th leading cause of death in women. Although most women respond initially to platinum-containing chemotherapy, 80% of women will relapse, become treatment resistance, and will die from this disease. These clinical outcomes led to the main theme of the Forbeck Forum “Challenges and Opportunities for Transformative Therapeutic Development for Ovarian Cancer” on March 11-12, 2022.   At this forum, transformative ways to target treatment resistance to PARPi resistance, immunotherapy, and chemotherapy (carboplatin, cisplatin, gemcitabine, and paclitaxel) were presented by known leaders in the field with the ultimate goal of improving outcomes of ovarian cancer patients.

To address resistance, we discussed key potential targets including:

• enhancing the immune system through a specific pathway called cGAS-STING (i.e., “innate” immunity) to recognize and eradicate ovarian tumor cells    
• epigenetics (not genetics), including DNA methylation and proteins that package DNA called histones, and bringing new epigenetic therapies into the ovarian cancer (OC) clinic

• targeting chemotherapy-induced cancer stem cells (CSCs), the small population of highly drug resistant cells that survive after chemotherapy, and ways to prevent enrichment of OCSCs
• employing immunotherapy combined with other therapeutics, including PARP inhibitors (PARPi) and epigenetic drugs (to “prime” the immune system), and the potential of starting these therapeutic approaches earlier during the course of OC treatment
• inhibiting DNA methylation to reduce evasion of OC cells by the immune system, using DNA methylation inhibitors to activate otherwise “repressed” elements that can cause immune signaling and enhance the innate immune system against ovarian tumor cells
• specific targets on the surface of OC cells (membrane receptors) and new drugs for these targets
• identifying how the origin of OC (ovarian surface epithelium vs fallopian tube epithelium cancer) may inform development of therapies

• biomarkers for response to PARPi,  mechanisms underlying resistance and overcoming resistance to PARPi and new clinical trials designed to expand the use of PARPi  
• novel mouse models that harbor common genetic changes found in human OC  
• therapeutic vulnerabilities based on metabolism of OC cells and the tumor microenvironment  

This forum was unique with the expertise of the participants in epigenetics, DNA repair, immunology, pathology, CRISPR (gene editing) technology, transposable elements and senescence. Additional expertise included basic scientists, translational scientists, mouse model system experts, and clinical trialists. This expertise led to robust and significant cross-expertise discussions such as how targeting epigenetics can affect the immune response that can then lead to smarter, more informative clinical trial design.  

Outcomes: Future projects and collaborations include the following:  

• How to identify response to immunotherapy through tertiary lymphoid structures (TLS) to correlate with improved survival
• How aging mouse models can be used to study tumor progression and the impact on the immune response
• How artificial intelligence may improve diagnosis and pathological changes in OC
• Sharing animal models of ovarian cancer between participants
• Sharing ovarian cancer tissue resources between participants (tissue microarrays)
• Sharing rare type cancer cell lines between participants
• Collaborations for multi-institutional clinical trials and grant applications have been discussed among participants
• Sharing genomic databases for exploration of research questions previously not addressed between participants

In summary, this forum has formed scientific and professional collaborations that will continue and will result in impactful papers, grants, and clinical trials.  

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Additional Updates – April 6, 2026

How has our field changed since the Forum?

1. Single-cell resolution technologies and digital spatial technologies that interrogate spatial biology, transcriptomics, metabolomics,and proteomics has provided a comprehensive understanding of the tumor microenvironment.
2. The first comprehensive pre-cancer atlas of fallopian tube precursors to high grade serous ovarian cancer is published (cbioportal data set available; PMID: 39704522).
3. Since the Forbeck seminar, there has been a slow but significant shift in the therapeutics. Specifically, a contraction of PARP inhibitor use and expansion of antibody driven approaches (antibody-drug conjugates) or cellular therapies (CAR T, CAR NK). Moreover, with the technology advancements the therapeutically targeting non-tumor cell compartment has come into focus.For instance, macrophages are supporting not only disease progression, but also reinforce immune suppression, thus strategies to “re-program” macrophages continue to gain traction in the pre-clinical space.
4. New targeted therapy: FDA approved ADC mirvetuximab soravtansinefor platinum-resistant ovarian cancer.

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Manuscripts Under Review (Forbeck Forum collaborators are in bold)

1. Ana Maria Isac, Andres Valdivia, Yinu Wang, Guangyuan Zhao, Chinmayee Prabhu Dessai, Ujin Kim, Sandra Orsulic, Ji-Xin Cheng, and Daniela Matei FABP4 Mediated Fatty Acid Transport Promotes Proliferation of Platinum-Resistant Ovarian Cancer Cells. Under review
2. Elizabeth R Woodruff, Courtney A Bailey, Francis To, Vyshnavi Manda,Joanne K Maltzahn, Timothy M Sullivan, Meher P Boorgula, Maria Sol Recouvreux, Ruby Vianzon, Bogi Conrad, Kathleen M Gavin, Kimberly R Jordan, Dwight J Klemm, Sandra Orsulic, Benjamin G Bitler, Zachary L Watson. Ablation of hematopoietic stem cell derived adipocytes reduces tumor burden in syngeneic mouse models of high-grade serous carcinoma. Under review

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Awards and Achievements

• Kenneth Nephew named Dean of the Ovarian Cancer Academy
• Sarah Adams named Dean of Ovarian Cancer Clinical Trial Academy
• Ben Bitler is involved in a SPORE team and is a co-investigator on an OCRA Health Equity Grant
• Yinu Wang received Early Career Investigator Award from OCRA
• Sandra Orsulic and Daniela Matei received a Collaborative VA Merit Grant to study platinum resistance in ovarian cancer
• Jose Conejo-Garcia received a DoD grant for the idea he presented at the Forbeck meeting - to investigate the formation of tertiary lymphoid structures in ovarian cancer, and clone antibodies as well as TCRs from histological sections with evidence of TLS
• Elisabeth Swisher has had multiple new appointments: Co-deputy Director of Fred Hutch/UW/Seattle Children’s Cancer Consortium; Elected to AAP; CurrentChair-elect of the AACR Cancer Prevention Working Group; Co-Chair of OvarianAACR meeting, 2023 and 2025

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What results have come from this Forum?

Jose-Conejo Garcia: We have also made progress on the clinical trial for patients with recurrent, chemo resistant ovarian cancer that I presented at the meeting, who are being treated with FSHR-targeted CAR T cells IP.  Nine patients have been treated and 2 of them have experienced significant clinical responses. One of them was injected with a second infusion of CART > a year after the initial remission.

Elizabeth Swisher: Completed enrollment on this IIT: NCT04673448 - Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary,Fallopian Tube, or Primary Peritoneal Cancer.

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Memories & Stories

Mazhar Adli: It was indeed one of the most useful and productive meetings I have attended. We have had multiple collaborative papers based on the ideas we discussed at that meeting.  For example, during coffee and lunch break discussions with Prof. Orsulic, we decided to collaborate and utilize her tissue microarrays (TMAs). This collaboration resulted in co-authorships in two impactful paper (above).   Similarly, Daniela and I have published several papers together since that meeting (above).

Benjamin Bittler: I look back on this meeting with fond memories!  First meeting in the midst of COVID, this meeting represented an incredible opportunity to reconnect with friends and develop new collaborations. I appreciated the forward thinking that the meeting afforded, using the breadth of existing ovarian cancer research we had the privilege of looking toward the next big discovery.

Jose Conejo-Garcia:  I have a great memory of that meeting.

Daniela Matei:  I also started many collaborations that continue to this day.  Collaborating with Sandra Orsulic and used resources and cell lines she generated.  Sandra helped me with a R01 grant that has been reviewed and revised a couple of times—it is still under review; she is aco-I on this grant. We also used tumors from Ken’s group, for a collaborative project that resulted in a paper about disparities in ovarian cancer. I am yet to get Kathy Cho’s mice, but it is on my list. I did get cell lines from Rugang Zhang for some experiments. Kate Chiapinelli  provided advice on computational analysis for ERVs on a study. I also have collaborated with Sharon Stack and she has provided me with critical professional advice and mentoring, when I needed it.  Yinu Wang received Early Career Investigator Award from OCRA.

Ken Nephew:  My first in person conference post-pandemic and a great way to "ease back into research life” after Covid.  I remember getting tested the first night of the conference!  Fond memories of dining together (big round tables), talking science and laughing together!  Collaborations fostered during the Forum resulted on co-authored publications with Daniela, Yinu, Heather, Fey, Steve and Ben; Paired platinum resistant HGS OC cell lines models from Daniela; Hosted Kathy Cho for Grand Rounds at IUSCCC;  Collaborative projects with Heather-New Co-PI awards from the Ovarian Cancer Alliance of Greater Cincinnati, submitted MPI R01 (will resubmit this year); Fey- submitted MPI R01 grant-  A1 to be submitted this year;  Steve and Fey- will submit SPORE renewal application this year- Fey & I Co-Lead OC Project in "Epigenetic Therapies New Advances" SPORE; Steve is the overall SPORE Co-PI and also Co-leads a project.  Rugang was Keynote Speaker at the Ovarian Cancer Academy Workshop- side note- Rugang first suggested that Daniela and I apply to Forbeck.  I was named Dean of the Ovarian Cancer Academy (Ronny Drapkin is Assistant Dean)and we received renewal this year (four more years) & Sarah named Dean of Ovarian Cancer Clinical Trial Academy: Future Deans of OCA and OCCTA attended the same Forbeck Forum- odds of that?!!

Sandra Orsulic: That was quite a conference! It felt like a family gathering where I was meeting long-lost cousins for the first time — familiar yet new, and truly inspiring. If the forum set out to unite bright minds with common interests in cancer, it absolutely delivered!

Fey Rassool:  I was relatively new to the ovarian cancer field and had a key opportunity to meet and interact with some of the luminaries in the ovarian cancer field. In particular, interactions with Rugang Zhang and Kate Chiapinelli  definitely led to publication of a stronger paper in ovarian cancer. Key to publishing our paper was also connecting with Daniela Matei, who helped us reexamine her RNA seq data from a recent clinical trial in ovarian cancer. Finally, my talk on STING in ovarian cancer subtypes at the Forbeck has also led to collaboration with Ken Nephew on STING agonists in this disease.

Sharon Stack: That was a great meeting!  What I talked about at the meeting is now published. In a follow-up that we're preparing to submit, targeting SREBP1 in combo with SOC therapy delays recurrence in high fat diet mice. Daniela has given our group lots of advice on dosing strategies for our murine experiments, both  carbopt/paclitaxel and olaparib.  Several good conversations with Steve Baylin on all things scientific. Also still thinking about Kathy Cho's mice (and actually just emailed her about them last week!) as soon as I can find some funding!

Rugang Zhang: It was indeed a very memorable meeting, and I learnt so much from everyone.  I have ongoing collaborations with Ben Bitler, Jose Conejo-Garcia and Sara Adams. The concept of targeting epigenetic regulators to overcome therapy-resistance presented in the meeting resulted in a project in MD Anderson ovarian cancer SPORE.

Liz Swisher:  I have had a lot of conversations about Kathy’s mice and sent several young investigators her ways for collaboration. And she was recently our keynote speaker for annual  UW WRHR retreat. Many collaborative publications and accomplishments (above).