Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma

Yu Cao, Michael Roth, Sajida Piperdi, Kristofer Montoya, Rebecca Sowers, Pulivarthi Rao, David S. Geller, Peter Houghton, E. Anders Kolb, Jonathan Gill, Richard Gorlick

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Survival outcomes for patients with osteosarcoma (OS) have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R) is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy. Methods: IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1-20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models. Results: IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy. Conclusions: IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.

Original languageEnglish (US)
Article numbere106249
JournalPLoS One
Volume9
Issue number8
DOIs
StatePublished - Aug 29 2014

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Somatomedin Receptors
osteosarcoma
Somatomedins
Osteosarcoma
therapeutics
antibodies
Antibodies
Tumors
Heterografts
Therapeutics
neoplasms
Messenger RNA
Neoplasms
insulin-like growth factor I receptor
clinical trials
Cells
cell lines
mutation
Polymerase Chain Reaction
Mutation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cao, Y., Roth, M., Piperdi, S., Montoya, K., Sowers, R., Rao, P., ... Gorlick, R. (2014). Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma. PLoS One, 9(8), [e106249]. https://doi.org/10.1371/journal.pone.0106249

Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma. / Cao, Yu; Roth, Michael; Piperdi, Sajida; Montoya, Kristofer; Sowers, Rebecca; Rao, Pulivarthi; Geller, David S.; Houghton, Peter; Kolb, E. Anders; Gill, Jonathan; Gorlick, Richard.

In: PLoS One, Vol. 9, No. 8, e106249, 29.08.2014.

Research output: Contribution to journalArticle

Cao, Y, Roth, M, Piperdi, S, Montoya, K, Sowers, R, Rao, P, Geller, DS, Houghton, P, Kolb, EA, Gill, J & Gorlick, R 2014, 'Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma', PLoS One, vol. 9, no. 8, e106249. https://doi.org/10.1371/journal.pone.0106249
Cao, Yu ; Roth, Michael ; Piperdi, Sajida ; Montoya, Kristofer ; Sowers, Rebecca ; Rao, Pulivarthi ; Geller, David S. ; Houghton, Peter ; Kolb, E. Anders ; Gill, Jonathan ; Gorlick, Richard. / Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma. In: PLoS One. 2014 ; Vol. 9, No. 8.
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abstract = "Background: Survival outcomes for patients with osteosarcoma (OS) have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R) is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy. Methods: IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1-20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models. Results: IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy. Conclusions: IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.",
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AU - Sowers, Rebecca

AU - Rao, Pulivarthi

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