Statistics show that epithelial ovarian cancer remains the most deadly of all gynecologic tumors, and only 46% of patients will survive for at least 5 years after diagnosis. There is a number of reasons why ovarian cancer has such a poor prognosis. One reason is that due to lack of specific symptoms, the majority of women are diagnosed at advanced stages of ovarian cancer, where cancer cells have spread from the ovary to other tissues in the abdomen. Another is that the cancer cells which survived the surgery have become resistant to chemotherapy and cancer grows back. Treatment of advanced ovarian cancer is difficult. Although surgeons do their best to make sure that all the cancer cells are removed during surgery, it is always possible that a tiny group of cancer cells has been left behind. Giving chemotherapy following surgery helps to catch any remaining cancer cells and kill them. However, it is unlikely that cancer treatment will kill every single cancer cell in the body. In addition, as a result of mutation of certain genes in cancer cells, these cells become resistant to chemotherapy. If this happens ovarian cancer patients may receive a different type of treatment. Unfortunately, very often cancer cells develop a resistance to many drugs at the same time, which makes eradication of cancer very difficult or even not possible.
My overall research program is designed to understand the function of molecules that drive ovarian cancer growth and spreading to different tissues. We also study the genetic changes in cancer cells leading to chemotherapy resistance. In addition, to ensure that we have the correct tools to study ovarian cancer as it exists in real patients, in the Bieniasz Lab we generate the most innovative and clinically relevant ovarian tumor models called patient-derived xenografts (PDXs). These tumor models are derived directly from ovarian cancer patients undergoing therapy in the Stephenson Cancer Center in Oklahoma City. PDX tumor models faithfully represent the original patient tumor features such as histology, gene expression profile (activation and mutation of specific genes) and response/resistance to therapy. We use PDX tumor models to improve preclinical evaluation of new anti-cancer therapies towards more personalized medicine. Ultimately, we aim to advance the knowledge of the mechanisms of ovarian cancer progression and chemotherapy resistance to design new treatment strategies with the long-term goal of translation of these therapies into clinical practice.
Ovarian cancer is the fifth leading cause of cancer deaths among women, with the high-grade serous ovarian cancer (HG-SOC) subtype responsible for two-thirds of ovarian cancer deaths. While a majority of patients initially respond to first-line treatment, a large proportion eventually relapses and develops platinum-resistant disease. Individually-tailored treatment regimens directed towards key oncogenic drivers and/or the use of novel drug combinations to prevent/overcome platinum resistance are promising opportunities to combat this disease. My overall research program is designed to understand the mechanistic role of oncogenic drivers in cancer progression and resistance to therapy to generate more effective and personalized treatment options for ovarian cancer patients with the ultimate goal of translation of these therapies into clinical practice. Furthermore, to complement studies evaluating the function of tumor oncogenes and to develop the clinically-relevant therapy against the crucial tumor drivers, we are implementing one of the most faithful, preclinical models of human cancer, which are patient-derived xenografts (PDXs).
The role of Ron receptor kinase in progression and platinum-resistance of ovarian cancer
My research interests lie in understanding the mechanistic role of oncogenic drivers in ovarian cancer progression and resistance to therapy, with the particular focus on Ron receptor isoforms. It has been shown that 55-73% of ovarian carcinomas overexpress Ron receptor kinase, where its high expression correlates with shorter overall survival and constitute an unfavorable prognostic factor in platinum-resistant ovarian cancer patients. Work performed in our laboratory revealed that subset of epithelial ovarian tumors express truncated Ron receptor kinase known as short-form Ron (sfRon), which is constitutively active and highly oncogenic. Our studies demonstrated that sfRon is highly expressed in high-grade serous ovarian cancer, the most prevalent and deadly ovarian cancer subtype and contributes to robust ovarian cancer growth and spreading to surrounding tissues. Our further studies using a large cohort of high-grade serous ovarian cancer patients demonstrated that significantly more patients in cisplatin resistant group express high levels of Ron receptors, compared to patients in cisplatin sensitive group, which suggest, that high levels of Ron and/or sfRon contribute to platinum drugs resistance. Our ongoing research work aims to understand the mechanism through which sfRon promotes ovarian cancer progression and platinum resistance and validate novel therapeutic strategies to target sfRon in ovarian cancer.
Patient-derived ovarian cancer models
Cancer is a highly heterogeneous disease. Each tumor is as individual as the patient and continually evolves and adapts under the selective pressure of chemotherapy, which has a huge impact on the design of clinical trials. Ultimately, there is an urgent need to improve the ability to predict drug response in heterogeneous population of patients diagnosed with specific tumor type and to identify patients who are most likely to benefit from particular combinations of drugs. In recent years, it has been shown that patient-derived xenografts (PDXs) are one of the most clinically-relevant models of human cancer, which enable sophisticated pre-clinical analysis of drug efficacy and biomarker studies. Currently, through collaboration with Stephenson Cancer Center we are generating a panel of high-grade serous ovarian cancer PDXs from chemotherapy-sensitive and chemotherapy-resistant patients. Our newly developed PDX tumor models represent remarkably well the original patient tumor with the respect to histology and genetic profile. In Bieniasz lab we utilize ovarian PDX tumor models as clinically relevant tools to study function of tumor oncogenes and novel anti-cancer therapies.
M.S., Medical University of Lodz, Poland, 2006
Ph.D., Medical University of Lodz, Poland, 2008
Postdoctoral Fellow, Roswell Park Cancer Institute, Buffalo, NY, 2008-2010
Postdoctoral Fellow, Hunstman Cancer Institute, Salt Lake City, UT, 2010-2014
Senior Postdoctoral Fellow, Oklahoma Medical Research Foundation, 2014-2015
Honors and Awards
First Award Certificate for the best experimental presentation in the Oncology, XLIV Polish and II International Conference of Students’ Scientific Societies and Junior Doctors, Lodz, Poland, 2006
First Award for the Best Master’s Thesis, VIII Meeting of the College of Laboratory Medicine, Gdansk, Poland, 2007
First Place Poster Presentation Award, Cancer Research Symposium, Stephenson Cancer Center, University of Oklahoma, 2015
Ad Hoc reviewer for Cancer Research
Ad Hoc reviewer for Medical Oncology
Ad Hoc reviewer for Adaptive Medicine
Ad Hoc reviewer for BMC Cancer
Ad Hoc reviewer for PLoS ONE
Ad Hoc reviewer for Tumor Biology
Ad Hoc reviewer for DNA and Cell Biology
2018 - present Precision Medicine Planning Group
2016 – present Gynecologic Cancers Research Program at Stephenson Cancer Center, OK
2014 – present American Association for Cancer Research (AACR)
2014–2015 Postdoctoral Association (PDA), Oklahoma Medical Research Foundation
2011–2014 Utah Postdoctoral Association (UPDA), Huntsman Cancer Institute, University of Utah, UT
2008–2010 Association of Postdoctoral Scholars (APoDS), Roswell Park Cancer Institute, Buffalo, NY
Joined OMRF scientific staff in 2016
Drumond-Bock AL, Wang L, Wang L, Cybula M, Rostworowska M, Kinter M, Bieniasz M. Increased expression of BRD4 isoforms long (BRD4-L) and short (BRD4-S) promotes chemotherapy resistance in high-grade serous ovarian carcinoma. Genes Cancer 14:56-76, 2023 September, PMID: 37705995, PMCID: PMC10496930
Corbin JM, Georgescu C, Wang L, Wren JD, Bieniasz M, Xu C, Asch AS, Ruiz Echevarría MJ. An unbiased seed-based RNAi selection screen identifies small RNAs that inhibit androgen signaling and prostate cancer cell growth. Mol Ther Nucleic Acids 33:257-272, 2023 June, PMID: 37554515, PMCID: PMC10404560
Wang L, Cybula M, Rostworowska M, Wang L, Mucha P, Bulicz M, Bieniasz M. Upregulation of Succinate Dehydrogenase (SDHA) Contributes to Enhanced Bioenergetics of Ovarian Cancer Cells and Higher Sensitivity to Anti-Metabolic Agent Shikonin. Cancers (Basel) 14, 2022 October, PMID: 36291881, PMCID: PMC9599980
Wang L, Wang L, Cybula M, Drumond-Bock AL, Moxley KM and Bieniasz M (2020) Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor. Genes Cancer. 2020 Jul 22;11(3-4):106-121. PMID: 33488949, PMCID: PMC7805538
Elayapillai S, Ramraj S, Benbrook DM, Bieniasz M, Wang L, Pathuri G, Isingizwe ZR, Kennedy AL, Zhao YD, Lightfoot S, Hunsucker LA, Gunderson CC. Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer. Gynecol Oncol. 2020 Oct 29:S0090-8258(20)34018-X. PMID: 33131904.
Hossen MN, Wang L, Chinthalapally HR, Robertson JD, Fung KM, Wilhelm S, Bieniasz M, Bhattacharya R, Mukherjee (2020) Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome. P.Sci Adv. 2020 Jul 22;6(30). PMID: 32743073, PMCID: PMC7375829
Moxley KM, Wang L, Welm AL, Bieniasz M (2016) Short-form Ron is a novel determinant of ovarian cancer initiation and progression. Genes & Cancer. May;7(5-6):169-81. PMID: 27551332, PMCID: PMC4979590.
*This publication has been recognized and selected as a cover article for the Genes & Cancer Journal, volume 7: Issue 5-6, May 2016.
Bieniasz M, Radhakrishnan P, Faham N, De La O JP, Welm AL (2015) Pre-clinical efficacy of Ron kinase inhibitors alone and in combination with PI3K inhibitors for treatment of sfRon-expressing breast cancer patient-derived xenografts. Clin Cancer Res. Dec 15;21(24):5588-600. PMID: 26289070, PMCID: PMC4681594.
Liu X, Zhao L, DeRose Y, Lin Y, Bieniasz M, Eyob H, Buys SS, Neumayer L, Welm AL (2011) Short-form Ron promotes spontaneous breast cancer metastasis through interaction with phosphoinositide 3-kinase. Genes & Cancer; July; 2:7:753-762. PMID: 22207901, PMCID: PMC3218405.