Tumorgrafts as in vivo surrogates for women with ovarian cancer

Saravut (John) Weroha, Marc A. Becker, Sergio Enderica-Gonzalez, Sean C. Harrington, Ann L Oberg, Matthew J. Maurer, Sarah E. Perkins, Mariam AlHilli, Kristina A. Butler, Sarah McKinstry, Stephanie Fink, Robert Brian Jenkins, Xiaonan Hou, Kimberly R. Kalli, Karin M. Goodman, Jann N Sarkaria, Beth Y. Karlan, Amanika Kumar, Scott H Kaufmann, Lynn C. HartmannPaul Haluska

Research output: Contribution to journalArticle

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Abstract

Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics. Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice. Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient. Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment.

Original languageEnglish (US)
Pages (from-to)1288-1297
Number of pages10
JournalClinical Cancer Research
Volume20
Issue number5
DOIs
StatePublished - 2014

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Ovarian Neoplasms
Neoplasms
SCID Mice
Fallopian Tubes
Platinum
Research Design
Carcinoma
Recurrence
Drug Therapy
Mortality
Therapeutics
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Weroha, S. J., Becker, M. A., Enderica-Gonzalez, S., Harrington, S. C., Oberg, A. L., Maurer, M. J., ... Haluska, P. (2014). Tumorgrafts as in vivo surrogates for women with ovarian cancer. Clinical Cancer Research, 20(5), 1288-1297. https://doi.org/10.1158/1078-0432.CCR-13-2611

Tumorgrafts as in vivo surrogates for women with ovarian cancer. / Weroha, Saravut (John); Becker, Marc A.; Enderica-Gonzalez, Sergio; Harrington, Sean C.; Oberg, Ann L; Maurer, Matthew J.; Perkins, Sarah E.; AlHilli, Mariam; Butler, Kristina A.; McKinstry, Sarah; Fink, Stephanie; Jenkins, Robert Brian; Hou, Xiaonan; Kalli, Kimberly R.; Goodman, Karin M.; Sarkaria, Jann N; Karlan, Beth Y.; Kumar, Amanika; Kaufmann, Scott H; Hartmann, Lynn C.; Haluska, Paul.

In: Clinical Cancer Research, Vol. 20, No. 5, 2014, p. 1288-1297.

Research output: Contribution to journalArticle

Weroha, SJ, Becker, MA, Enderica-Gonzalez, S, Harrington, SC, Oberg, AL, Maurer, MJ, Perkins, SE, AlHilli, M, Butler, KA, McKinstry, S, Fink, S, Jenkins, RB, Hou, X, Kalli, KR, Goodman, KM, Sarkaria, JN, Karlan, BY, Kumar, A, Kaufmann, SH, Hartmann, LC & Haluska, P 2014, 'Tumorgrafts as in vivo surrogates for women with ovarian cancer', Clinical Cancer Research, vol. 20, no. 5, pp. 1288-1297. https://doi.org/10.1158/1078-0432.CCR-13-2611
Weroha, Saravut (John) ; Becker, Marc A. ; Enderica-Gonzalez, Sergio ; Harrington, Sean C. ; Oberg, Ann L ; Maurer, Matthew J. ; Perkins, Sarah E. ; AlHilli, Mariam ; Butler, Kristina A. ; McKinstry, Sarah ; Fink, Stephanie ; Jenkins, Robert Brian ; Hou, Xiaonan ; Kalli, Kimberly R. ; Goodman, Karin M. ; Sarkaria, Jann N ; Karlan, Beth Y. ; Kumar, Amanika ; Kaufmann, Scott H ; Hartmann, Lynn C. ; Haluska, Paul. / Tumorgrafts as in vivo surrogates for women with ovarian cancer. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 5. pp. 1288-1297.
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AU - Weroha, Saravut (John)

AU - Becker, Marc A.

AU - Enderica-Gonzalez, Sergio

AU - Harrington, Sean C.

AU - Oberg, Ann L

AU - Maurer, Matthew J.

AU - Perkins, Sarah E.

AU - AlHilli, Mariam

AU - Butler, Kristina A.

AU - McKinstry, Sarah

AU - Fink, Stephanie

AU - Jenkins, Robert Brian

AU - Hou, Xiaonan

AU - Kalli, Kimberly R.

AU - Goodman, Karin M.

AU - Sarkaria, Jann N

AU - Karlan, Beth Y.

AU - Kumar, Amanika

AU - Kaufmann, Scott H

AU - Hartmann, Lynn C.

AU - Haluska, Paul

PY - 2014

Y1 - 2014

N2 - Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics. Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice. Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient. Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment.

AB - Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics. Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice. Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient. Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment.

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