About

Fiona Simpkins, M.D., is the Hilarie L. and Mitchell L. Morgan President's Distinguished Professor in Women's Health at the University of Pennsylvania. She serves as an Attending Physician in Gynecologic Oncology at the Department of Ob/Gyn, Hospital of the University of Pennsylvania, and Pennsylvania Hospital, and is actively involved in clinical practice and research within gynecologic oncology. Dr. Simpkins is the Director of Clinical & Translational Gynecologic Oncology Research at Penn Medicine Health System. Her educational background includes a B.S. in Biology from the University of California, Los Angeles, obtained in 1993, and an M.D. from Temple University School of Medicine in 1999. Her professional focus encompasses women's health, gynecologic oncology, and translational research aimed at improving outcomes for women with gynecologic cancers.

Research topics

• Medicine
• Cancer research
• Internal medicine
• Oncology
• Biology

Selected publications

• Combination ATR and PARP Inhibitor (CAPRI) trial in recurrent platinum-sensitive high-grade serous ovarian cancer demonstrates activity independent of homologous recombination repair status

  Gynecologic Oncology · 2026-04-23

  article1st authorCorresponding
  PublisherDOI

• Combination of exportin-1 (XPO1) with Bcl-2/xL inhibition is synergistic in low-grade serous ovarian cancer

  Gynecologic Oncology · 2026-04-23

  articleSenior author
  PublisherDOI

• Abstract 7749: Increased immune activity in patients with high-grade serious ovarian cancer after combination PARPi + ATRi therapy

  Cancer Research · 2026-04-03

  articleSenior author

  Abstract Introduction: Complete responses to PARP inhibitor (PARPi) monotherapy in recurrent high-grade serous ovarian cancer (HGSOC) are rare. However, preclinical data have demonstrated promising synergy between PARP and ATR inhibitors. Characterizing the immune contexture of the tumor microenvironment and the surrounding stroma during treatment may provide valuable biological insights into the efficacy of this combination therapy and inform future combinations. Methods: Patients with recurrent HGSOC received ceralasertib 160mg orally daily, days 1-7 and olaparib 300mg twice daily, days 1-28 of a 28-day cycle. 18 tissue samples were collected across archival (resection) and pre-treatment and on-treatment timepoints (core biopsies). Each sample was analyzed using a 25-plex multiplex immunohistochemistry (mIHC) assay, which interrogates cell composition and functional states of neoplastic and immune cell types, including all major lymphoid and myeloid populations. Segmented cells were assigned to either a tumor or stroma compartment using a PanCK mask that was uniformly expanded by 25μm, and average cell densities were calculated for each compartment. Results: Samples obtained during combination PARPi + ATRi treatment demonstrated widespread increases in immune cell densities including T cells (CD8+, Tregs, and Th1-like cells), B cells, dendritic cells, macrophages, and monocytes. Among the T-cell populations, higher densities of Granzyme B and PD-1 were observed, indicating enhanced cytotoxic activity and immune engagement. Concurrently, there was a decrease in proliferating neoplastic cells (PanCK+Ki67+), consistent with reduced tumor cell proliferation during treatment. Using the PanCK tumor mask, we observed that CD8+ T cells, Th1-like cells, B cells, and dendritic cells increased more prominently within the tumor compartment compared to the surrounding stroma. Samples obtained prior to treatment from patients with stable or progressive disease (SD/PD) exhibited higher macrophage densities, primarily attributable to elevated levels of M2-like (immunosuppressive) macrophages. Conclusions: The increased immune cell densities measured by mIHC indicate overall activation of the immune system following PARPi + ATRi treatment. Elevated levels of PD-1+ and Granzyme B+ T cells suggest enhanced immune activation and cytotoxic potential, while comparative analysis of the tumor versus stroma compartments demonstrates improved immune cell infiltration into the tumor. Notably, higher baseline densities of M2-like macrophages may influence or limit response to therapy. Collectively, these findings provide evidence that PARPi + ATRi combination therapy promotes anti-tumor immune activity. However, additional data is needed to correlate these immune changes with clinical outcomes. Citation Format: Elias Pavlatos, Benjamin Tate, Austin Nguyen, Ian S. Heller, Dimitrios Nasioudis, Janos L. Tanyi, Drew A. Torigian, Diego Rodriguez, Susan M. Domchek, Ronny I. Drapkin, Eric J. Brown, Gordon B. Mills, Fiona Simpkins. Increased immune activity in patients with high-grade serious ovarian cancer after combination PARPi + ATRi therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7749.

  PublisherDOI

• Abstract 1052: Real-world treatment patterns and outcomes reveal distinct clinical trajectories of patients with Cyclin E1-positive ovarian cancer

  Cancer Research · 2026-04-03

  article

  Abstract Background: The success of novel therapies as they progress in later phases of clinical development requires accurate benchmarking of the benefit provided by the standard of care (SOC) at the time of clinical study completion. Information collected from published investigational studies or retrospective registries can be outdated or may not reflect the most current SOC. Furthermore, the development of novel agents, especially for patients on later lines of treatment, may be restricted to select populations, not previously characterized in the literature, perhaps defined by criteria such as a novel biomarker (e.g. Cyclin E1 positive tumors) or narrow indication sub-types (e.g., platinum resistant ovarian cancer with less than N prior therapy lines). Here, we demonstrate how the analysis of Real-World Data (RWD), as well as screening data — collected in the context of recent early phase clinical studies — is guiding development of the WEE1 inhibitor azenosertib in Cyclin E1 positive high grade serous ovarian cancer (HGSOC). Methods: The records of medications and lines of therapy were curated from Tempus Lens (TLOv) or Zentalis Retrospective Study of Early Treatment (ReSET) cohorts. Outcomes such as best response, progression free survival and treatment free survival were evaluated for patient subsets defined by treatment history or Cyclin E1 expression status from RNA sequencing (for TLOv) or protein immunohistochemistry (IHC for ReSET) after benchmarking RNA-based classification using independent HGSOC tissues (N=92). Results: Compared to IHC, RNA-based Cyclin E1 classification was > 70% accurate, with higher rates of False Negative than False Positives, providing an acceptable surrogate to stratify patients in the TLOv cohort. The treatment regimens used in early lines were consistent between TLOv and ReSET cohorts and reflected current SOC, including partial use of PARPi in 1L maintenance and a preference for doxorubicin-based regimens in 2L for platinum-resistant patients. The data confirmed previous observations that BRCA-mutated patients had better prognosis, likely due to PARPi treatment eligibility after 1L. Patients with Cyclin E1 positive tumors were observed in both platinum-resistant and platinum-sensitive settings, with a higher prevalence in platinum-resistant setting. Patients with Cyclin E1 positive tumors had worse outcomes in 1L, or with selected treatment regimens in subsequent lines, highlighting their consistent unmet need throughout the entire treatment journey. Conclusions: RWD represents a reliable and up-to-date source of treatment and outcomes information for HGSOC patients. Clean identification of lines and intent of treatment as well as availability of direct or surrogate Cyclin E1 expression status were key to highlighting the unmet need of patients with Cyclin E1 positive tumors, informing azenosertib’s development. Citation Format: Jinkil Jeong, Mona Abed, Catherine Lee, Heekyung Chung, Alexandra Levy, Nandini Molden, Divya Rajendran, Joyce F. Liu, Leslie M. Randall, Fiona Simpkins, Funda Meric-Bernstam, Danielle D. Jandial, Doris Kim, Olivier Harismendy. Real-world treatment patterns and outcomes reveal distinct clinical trajectories of patients with Cyclin E1-positive ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1052.

  PublisherDOI

• Results of integrating an automated electronic social determinants of health screening survey in a gynecologic oncology practice: a pilot study

  International Journal of Gynecological Cancer · 2026-02-25

  article
  PublisherDOI

• Abstract A133: Target clear cell ovarian cancers with ARID1A loss by combination inhibition of BRD4 and ATR

  Molecular Cancer Therapeutics · 2025-10-22

  articleSenior author

  Abstract Background: Clear cell ovarian cancer (CCOC) is often resistant to standard chemotherapy and has limited treatment options in the advanced or recurrent setting. ARID1A is the most prevalent mutation, with approximately 50% of all CCOC harboring this mutation. ARID1A, a member of the SWI/SNF family, regulates transcription and has a major role in the repair of DNA lesions, directly facilitating DNA accessibility on the chromatin or indirectly by facilitating the functions of DNA repair proteins. We propose that CCOCs unique genomic alterations (e.g., ARID1A frameshift or nonsense mutations) will increase dependency on chromatin remodeling and DNA repair (e.g., ATR/CHK1/WEE1) pathways for survival. We hypothesize that combination of low-dose small-molecule inhibitors of the BET family (BRD4i) and the DNA damage repair pathway (ATR/CHK1/WEE1), will especially target ARID1A mutant cancer cells promoting mitotic catastrophe, apoptosis, and tumor regression, sparing normal cells. Method: Use a small size drug screen, we tested and compared drugs’ efficacy in ARID1A mutant cells with wildtype lines. The efficacy of BRD4i combination with either ATRi or WEE1i were evaluated in ARID1A mutant/wildtype lines, and also knockdown or knockout cells compared with isogenic parental lines. The drugs combination affecting the transcription regulation, cell cycle, homologous recombination, apoptosis, and DNA damage were investigated. A CCOC preclinical drug development patient-derived xenograft (PDX) platform was established and drugs’ combinations were evaluated in ARID1A mutant and ARID1A wild-type (ARID1A MUT and ARID1A WT) PDX models. Results: Through the small size of drug screen, we identified that BRD4i, ATRi and WEE1i are more effective in ARID1A mutant cells comparing to that in wildtype lines. Low-dose combination of BRD4i with DNA damage repair inhibitors, ATRi/WEE1i (BDR4i-ATRi or BRD4i-WEE1i), were synergistic in decreasing survival and colony formation in ARID1A MUT cells compared to ARID1A WT. Both combinations showed significant tumor regression and increased overall survival compared to standard chemotherapy or monotherapy in several ARID1A MUT PDX models but minimal in an ARID1A WT PDXs. Among BRD4i-DDRi combinations, BRD4i-ATRi is superior to BRD4i-WEE1i in terms of antitumor effect and drug tolerability. BRD4i-ATRi caused a robust G1 arrest. The BRD4i-ATRi treatment defects homologous recombination and leads to an increase in DNA double-strand breaks and cell apoptosis in the ARID1A MUT or knockout cells. Conclusion: Our studies identify a novel drug combination targeting a genetic alteration (e.g., ARID1A) common in CCOC that is highly effective and tolerable. BRD4i in combination with ATRi or WEE1i was synergistic in vitro in ARID1A MUT models. Using our novel CCOC drug development PDX platform, we demonstrated that BRD4i-ATRi combination therapy is more effective than standard chemotherapy or monotherapy alone with acceptable toxicity in ARID1A MUTPDXs. Citation Format: Yasuto Kinose, Haineng Xu, Hyoung Kim, Xiaolei Wang, Sushil Kumar, Xiaoyin Shan, Erin George, Sergey Medvedev, Amaryllis Ortiz, Sarah Gitto, Margaret Whicker, Kurt D'Andrea, Bradley Wubbenhorst, Dorothy Hallberg, Mark O'Connor, Lauren Schwartz, Wei-Ting Hwang, Katherine L. Nathanson, Gordon Mills, Victor E. Velculescu, Tian-Li Wang, Eric Brown, Ronny Drapkin, Fiona Simpkins. Target clear cell ovarian cancers with ARID1A loss by combination inhibition of BRD4 and ATR [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A133.

  PublisherDOI

• Supplemental Figure S5 from [<sup>18</sup>F]FluorThanatrace ([<sup>18</sup>F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study

  2025-11-25

  articleOpen accessSenior author

  <p>Clinical response correlates.</p>

  PublisherOA PDFDOI

• Supplementary Figure 1 from Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) Trial in Acquired PARP Inhibitor–Resistant Homologous Recombination–Deficient Ovarian Cancer

  2025-11-25

  articleOpen accessSenior author

  <p>Trial schema</p>

  PublisherDOI

• Clinical trial protocol1 from Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) Trial in Acquired PARP Inhibitor–Resistant Homologous Recombination–Deficient Ovarian Cancer

  2025-11-25

  articleOpen accessSenior author

  <p>Trial protocol</p>

  PublisherDOI

• Supplemental Figure S6 from [<sup>18</sup>F]FluorThanatrace ([<sup>18</sup>F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study

  2025-11-25

  articleOpen accessSenior author

  <p>18F]FTT-PET on subject previously treated with PARPi.</p>

  PublisherOA PDFDOI

Recent grants

• NIH Grant K08CA151892

  NIH · $807k · 2017

• A novel more effective genotoxic therapy for ovarian cancer

  NIH · $2.6M · 2023–2026

• Project 3: Investigating new treatment approaches based on DNA repair vulnerability in ARID1A mutated type I ovarian cancer

  NIH · $31.7M · 2018–2029

Frequent coauthors

• Hyoung Kim

  135 shared

• Nawar Latif

  122 shared

• Sarah B. Gitto

  Cancer Research Center

  110 shared

• Eric J. Brown

  102 shared

• Gordon B. Mills

  OHSU Knight Cancer Institute

  97 shared

• Mark A. Morgan

  82 shared

• Joseph A. Lucci

  82 shared

• Dimitrios Nasioudis

  University of Pennsylvania

  82 shared

Labs

• Fiona Simpkins LaboratoryPI

Awards & honors

• Hilarie L. and Mitchell L. Morgan President's Distinguished…