NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use

Gwen McCaffrey, Michelle L. Thompson, Lisa Majuta, Michelle N. Fealk, Stephane Chartier, Geraldine Longo, Patrick W Mantyh

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Studies in animals and humans show that blockade of nerve growth factor (NGF) attenuates both malignant and nonmalignant skeletal pain. While reduction of pain is important, a largely unanswered question is what other benefits NGF blockade might confer in patients with bone cancer. Using a mouse graft model of bone sarcoma, we demonstrate that early treatment with an NGF antibody reduced tumor-induced bone destruction, delayed time to bone fracture, and increased the use of the tumor-bearing limb. Consistent with animal studies in osteoarthritis and head and neck cancer, early blockade of NGF reduced weight loss in mice with bone sarcoma. In terms of the extent and time course of pain relief, NGF blockade also reduced pain 40% to 70%, depending on the metric assessed. Importantly, this analgesic effect was maintained even in animals with late-stage disease. Our results suggest that NGF blockade immediately upon detection of tumor metastasis to bone may help preserve the integrity and use, delay the time to tumor-induced bone fracture, and maintain body weight.

Original languageEnglish (US)
Pages (from-to)7014-7023
Number of pages10
JournalCancer Research
Volume74
Issue number23
DOIs
StatePublished - Dec 1 2014

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Bone Neoplasms
Bone Development
Nerve Growth Factor
Extremities
Bone and Bones
Pain
Bone Fractures
Sarcoma
Neoplasm Antibodies
Neoplasms
Head and Neck Neoplasms
Osteoarthritis
Analgesics
Weight Loss
Body Weight
Neoplasm Metastasis
Transplants

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use. / McCaffrey, Gwen; Thompson, Michelle L.; Majuta, Lisa; Fealk, Michelle N.; Chartier, Stephane; Longo, Geraldine; Mantyh, Patrick W.

In: Cancer Research, Vol. 74, No. 23, 01.12.2014, p. 7014-7023.

Research output: Contribution to journalArticle

McCaffrey, Gwen ; Thompson, Michelle L. ; Majuta, Lisa ; Fealk, Michelle N. ; Chartier, Stephane ; Longo, Geraldine ; Mantyh, Patrick W. / NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use. In: Cancer Research. 2014 ; Vol. 74, No. 23. pp. 7014-7023.
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