Research Summary:
Understand the biology of ovarian cancer invasion and metastasis and identify novel targets for treatment

The laboratory is dedicated to improving our understanding of the biology of ovarian cancer metastasis and to exploring the use of novel drugs for its treatment. Ovarian cancer is the 5th leading cause of cancer death among women in the United States, and has the highest mortality rate of all gynecologic malignancies. The high fatality of the disease is because it is often diagnosed at a late stage, when tumor cells have disseminated within the peritoneal cavity.
After the malignant transformation of ovarian surface epithelial cells and the growth of the tumor within the ovary, tumor cells detach from the ovary and attach to the peritoneum or omentum, but rarely leave the peritoneal cavity Despite aggressive treatment more than two thirds of all patients succumb to their disease within 5 years.
See our review article on ovarian cancer in the American Journal of Pathology (Sept. 2010). See "Rethinking ovarian cancer: recommendations for improving outcomes" Nature Reviews Cancer (Oct., 2011), which contains proposals by an international group of researchers that included Dr. Lengyel. We also recently published a summary of Epithelial ovarian cancer experimental models in Oncogene (Auguest 2013).

Main projects in the laboratory:

  1. Understand the early steps of ovarian cancer metastasis to the peritoneum and omentum and characterize tumor – stroma interactions in ovarian cancer metastasis
  2. Characterize new treatment targets and test them in pre-clinical models. Recent work from our lab has shown that c-Met might be a good treatment target for breast and ovarian cancer
  3. Investigate new agents that may delay or inhibit the development of ovarian cancer
  4. Study the role of miRNA’s in ovarian cancer metastasis

In our research we use primary and cultured ovarian cancer cell lines and mouse models of ovarian cancer (xenograft, genetic). Interactions between cancer cells and the microenvironment are investigated using confocal microscopy (see our movie of a novel co-invasion assay). We have also assembled 10 tissue micro arrays (200 patients) with tissue from primary and metastatic ovarian cancers. These tissue samples are linked to an ACCESS database containing clinico-pathologic information on all ovarian cancer patients operated on at the University of Chicago since 1992. Data are collected prospectively.
We cooperate very closely with the Department of Pathology at the University of Chicago, particularly with two Gynecologic Pathologists, Drs. Montag and Krausz. Other important collaborators are Dr. Marcus Peter in the Division of Hematology/Oncology at Northwestern University, Dr. Joe Piccirilli from the Department of Biochemistry and Molecular Biology and Dr, Kay Macleod, in the Ben May Department of Cancer Research. A very close collaborator whose office is actually next to mine is Dr. Iris Romero, who works on ovarian cancer prevention.
I am an Obstetrician and Gynecologist and a Gynecologic Oncologist, with a special clinical focus on the surgical treatment of ovarian cancer and a scientific focus on the biology of ovarian cancer. Click here for an interview in which I discuss my ovarian cancer research. Ultimately, we hope to realize the major goal of the laboratory; to translate our findings and understanding of ovarian cancer tumor biology into novel therapeutic treatments that will improve the survival of those with this devastating disease. Our research is funded by the NIH, the Ovarian Cancer Research Foundation, and the Gynecologic Cancer Foundation.

Ernst Lengyel
April, 2014

  nature medicine cover

Kristin M Nieman, Hilary A Kenny, Carla V Penicka, Andras Ladanyi, Rebecca Buell-Gutbrod, Marion R Zillhardt, Iris L Romero, Mark S Carey, Gordon B Mills, Gökhan S Hotamisligil, S Diane Yamada, Marcus E Peter, Katja Gwin & Ernst Lengyel. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth Nat Med. 2011 Oct 30;17(11):1498-503

Ovarian tumors preferentially metastasize to the omentum, a peritoneal fat layer. This report proposes that the reasons for this predilection stem from the growth advantage conferred by adipocytes on ovarian cancer cells. Adipocytes seem to promote homing of cancer cells through adipokine secretion, and direct contact of the two cell types promotes metabolic changes that result in lipid transfer from adipocytes to tumor cells. Environmental-driven metabolic adaptations could be exploited to target omental metastasis

  MCT civer Zhang Y, Kenny HA, Swindell EP, Mitra AK, Hankins PL, Ahn RW, Gwin K, Mazar AP, O'Halloran TV, Lengyel E.

Urokinase plasminogen activator system-targeted delivery of nanobins as a novel ovarian cancer therapy.
Mol Cancer Ther. 2013 Dec;12(12):2628-39

An image from the paper was selected for the cover. See Abstract

 


The Cover of the October 2007 International Journal of Cancer
displays a picture of the 3D omental metastasis model created by the Lengyel Lab

Kenny HA, Krausz T, Yamada SD, Lengyel E. Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian cancer cells. Int J Cancer 2007;121:1463-72.


Zillhardt M, Christensen JG, Lengyel E,.An orally available small-molecule inhibitor of c-Met, PF-2341066, reduces tumor burden and metastasis in a preclinical model of ovarian cancer metastasis. Neoplasia 2010, 12:1-10

Dr. Lengyel
Principal Investigator
Ernst Lengyel, MD, PhD
Professor,
Section of Gynecologic Oncology
Department of Obstetrics & Gynecology The University of Chicago

Contact information:

Laboratory Tel.: (773) 702 9763
Office Tel.: (773) 702 6722
Clinical appointments: (773) 702 6123
Email: elengyel@uchicago.edu

Geri Cooper, Academic Assistant


Laboratory Location:

Gordon Center for Integrative Science
929 E. 57th St.
1st floor: Rms W106 (office) and W107 (lab)
Chicago, Illinois 60637, USA

See map

If you are a patient please contact our clinical ovarian cancer care group:
OvarianCancer@uchicago.edu

Location for outpatient visits:
Center for Advanced Medicine
5758 S. Maryland Avenue
Chicago, IL 60637
See map

Clinical Bio

Ovarian Cancer Treatment at The University of Chicago Medicine

Mailing address:
Ernst Lengyel, MD, PhD
Department of OBGYN, MC 2050
Chicago, Ill. 60637, USA

Committee on Cancer Biology Web page

Link to the Ovarian Cancer Research Fund

In the News

Watch the Society of Gynecologic Oncology video about the University of Chicago Gynecologic Cancer Care Team

BBC Health News report on the Lengyel Lab research published in the Nov. 2011 Nature Medicine
Further reports in:
Nature Outlook
Cancer Discovery
US News & World Report

Article in the L.A. Times about the Chicago Cancer Geonome Project