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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-12, Vol.74 (23), p.7014-7023
• Main Authors: McCaffrey, Gwen, Thompson, Michelle L, Majuta, Lisa, Fealk, Michelle N, Chartier, Stephane, Longo, Geraldine, Mantyh, Patrick W
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - pharmacology; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Line, Tumor; Disease Models, Animal; Extremities - pathology; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Male; Mice; Mice, Inbred C3H; Neoplasm Metastasis; Nerve Growth Factor - antagonists & inhibitors; Nerve Growth Factor - metabolism; Nerve Growth Factors - antagonists & inhibitors; Nerve Growth Factors - metabolism; Osteoarthritis - drug therapy; Osteoarthritis - metabolism; Osteoarthritis - pathology; Pain - drug therapy; Pain - metabolism; Random Allocation; Sarcoma - drug therapy; Sarcoma - metabolism; Sarcoma - pathology
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-14-1220

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.