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 are a number of reasons for 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 cancer 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 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 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
Honors and Awards
2015 First Place Poster Presentation Award, 2015 Cancer Research Symposium, Stephenson Cancer Center, University of Oklahoma
2007 First Award for the Best Master’s Thesis, VIII Meeting of the College of Laboratory Medicine, Gdansk, Poland
2006 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
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
2016 – present: Member, 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
Bieniasz M, Radhakrishnan P, Faham N, De La O JP, Welm AL. Preclinical 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 21:5588-600, 2015 December, PMID: 26289070, PMCID: PMC4681594
Gil M, Bieniasz M, Seshadri M, Fisher D, Ciesielski MJ, Chen Y, Pandey RK, Kozbor D. (2011) Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumors in mice. Br J Cancer 8:105, 2011 Nov, PMID: 21989183, PMCID: PMC3242530
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
Gil M, Bieniasz M, Wierzbicki A, Bambach BJ, Rokita H, Kozbor D. (2009) Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic cells to prime specific CD8+ T cell responses in tumor-bearing mice. J Immunol. Nov; 15;183(10):6808-18. PMID: 19846865 PMCID: PMC2805007
Bieniasz M, Oszajca K, Eusebio M, Kordiak J, Bartkowiak J, Szemraj J. (2009). The positive correlation between gene expression of the two angiogenic factors: VEGF and BMP-2 in lung cancer patients. Lung Cancer. Dec;66(3):319-26. PMID: 19324447
Jamroziak K, Szemraj Z, Grzybowska-Izydorczyk O, Szemraj J, Bieniasz M, Cebula B, Giannopoulos K, Balcerczak E, Jesionek-Kupnicka D, Kowal M, Kostyra A, Calbecka M, Wawrzyniak E, Mirowski M, Kordek R, Robak T. (2009). CD38 gene polymorphisms contribute to genetic susceptibility to B-cell chronic lymphocytic leukemia: evidence from two case-control studies in Polish Caucasians. Cancer Epidemiol Biomarkers Prev. Mar;18(3):945-53. PMID: 19240243
Bieniasz M, Bartkowiak J, Szemraj J. (2008). Gene expression of bone morphogenetic proteins, matrix metalloproteinases and inhibitors of matrix metalloproteinases in lung cancers and their prognostic significance. Postepy Biochem. 54(1):82-90. PMID: 19846865 PMCID: PMC2805007
Oszajca K, Bieniasz M, Brown G, Swiatkowska M, Bartkowiak J, Szemraj J. Effect of oxidative stress on the expression of t-PA, u-PA, u-PAR, and PAI-1 in endothelial cells. Biochem Cell Biol. 2008 Dec;86(6):477-86. PMID: 19088796
Functional and Genomics Research Program, MS 46
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2155
Fax: (405) 271-3765