Dr. Kostenuik began his research career as a PhD student studying tumor
cell invasion and metastasis, followed by a post-doctoral fellowship on
the pathophysiology of glioblastoma. His focus on oncology continued
with 15 years of preclinical and clinical research on cancer metastasis
at Amgen. In 1999 Paul received an ASBMR award for his research
on novel treatments for hypercalcemia of malignancy
(PMID: 10706080*, below), which culminated in 2014
with an FDA treatment indication for Xgeva®.
Oncology
Some of Dr. Kostenuik's
publications in
the oncology field:
A quantitative model for spontaneous bone metastasis: Evidence for a mitogenic effect of bone on Walker 256 cancer cells. Kostenuik PJ, Singh G, Suyama KL, and Orr FW. Clin Exp Metastasis 10: 403-410, 1992.
PMID: 1451350
Stimulation of bone resorption results in a selective increase in the growth rate of spontaneously metastatic Walker 256 cancer cells in bone. Kostenuik PJ, Singh G, Suyama KL, and Orr FW. Clin Exp Metastasis 10: 411-417, 1992. PMID: 1451351
Mechanisms involved in the metastasis of cancer to bone. Orr FW, Kostenuik PJ, Sanchez-Sweatman OH, and Singh G. Breast Cancer Res Treatment 25: 151-163, 1993. PMID: 8347847
Increased growth rate and tumor burden of spontaneously metastatic Walker 256 cancer cells in the skeleton of bisphosphonate-treated rats. Kostenuik PJ, Orr FW, Suyama KL, and Singh G. Cancer Res 53: 5452-5457, 1993.
PMID: 8221685
Increased expression of C-myc messenger-RNA and protein in Walker 256 cancer cells stimulated by bone-derived conditioned media and by transforming growth factor-β. Kostenuik PJ, Orr FW, Arsenault L, Millar-Book W, and Singh G. Int J Oncol 3: 729-734, 1993. PMID: 21573425
Tumor-bone interactions in skeletal metastasis. Orr FW, Sanchez-Sweatman OH, Kostenuik PJ, and Singh G.
Clin Orthop Rel Res 312: 19-33, 1995. PMID: 7634602
Bone cell matrix promotes the adhesion of human prostatic carcinoma cells via the α2β1 integrin. Kostenuik PJ, Sanchez-Sweatman O, Orr FW, and Singh G. Clin Exp Metastasis 14: 19-26, 1996. PMID: 8521612
Potential roles for adhesion in the pathogenesis of bone metastasis. Kostenuik PJ. In: Mechanisms and Pathophysiology of Bone Metastasis. Edited. by F.W. Orr, R.G Landes Biomedical Publishers, Austin, TX, 1996.
pp. 59-75.
Transforming growth factor β upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen: Implications for the pathogenesis of bone metastasis. Kostenuik PJ, Singh G, and Orr FW. Clin Exp Metastasis 15: 41-52, 1997. PMID: 9009105
Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy. Capparelli C, Kostenuik PJ, Morony S, Starnes C, Weimann B, Lacey DL, and Dunstan CR. Cancer Res 60: 783-787, 2000. PMID: 10706080*
Mechanisms of tumor metastasis to bone. Weber MH, Goltzman D, Kostenuik PJ, Rabbani S, Singh G, Tozer R and Orr FW. Critical Rev Eukaryotic Gene Expression 10: 281-302, 2000. PMID: 11272470
Osteoprotegerin: A potential novel therapeutic agent for treatment of humoral hypercalcemia of malignancy. Capparelli C, Kostenuik PJ. Cancer Res Alert 2: 22-24, 2000.
Osteoprotegerin (OPG) decreases skeletal tumor burden and inhibits osteolysis in murine models of experimental bone metastasis. Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR and Kostenuik PJ. Cancer Res 61: 4432-4436, 2001. PMID: 11389072
Serum osteoprotegerin levels are increased in patients with advanced prostate cancer. Brown JM, Vessella RL, Kostenuik PJ, Dunstan CR, Corey E. Clin Cancer Res 7: 2977-83, 2001. PMID: 11595685
The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft.Kiefer JA, Vessella RL, Quinn JE, Odman AM, Zhang J, Keller ET, Kostenuik PJ, Dunstan CR and Corey E. Clin Exp Metastasis 21: 381-387, 2004. PMID: 15672862
OPG, RANK and RANKL in bone metastasis and cancer-associated osteolysis. Kostenuik PJ. In: Bone Metastasis and Molecular Mechanisms - Pathophysiology. Edited by G. Singh and F.W. Orr, Kluwer Academic Publishers, Boston, MA, 2004. pp 211-240.
Revisiting the seed and soil theory of bone metastasis: New tools, same answer. Kostenuik PJ. J Musculoskel Neuron Interact 4: 375-376, 2004. PMID: 15758267
Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases. Morrissey C, Kostenuik PJ, Brown LG, Vessella RL, Corey E. BMC Cancer 7:148, 2007. PMID: 17683568
Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, Dougall WC. Clin Exp Metastasis 25: 119-129, 2008. PMID: 18064531
The development of denosumab for the treatment of bone loss and cancer-induced bone destruction. Goessl C, Katz L, Dougall WC, Kostenuik PJ, Zoog HB, Braun A, Dansey R, and Wagman RB. Annals NY AcadSci 1263: 29-40, 2012. PMID: 22831177
Hypocalcemia in patients with metastatic bone disease treated with denosumab. Body JJ, Bone HG, deBoer RH, Stopeck A, van Poznak C, Damiao R, Fizasi K, Henry DH, Ibrahim T, Lipton A, Saad F, Shore N, Takano T, Shaywitz A, Wang H, Bracco O, Braun A, and Kostenuik PJ. Eur J Cancer 51: 1812-1821, 2015. PMID: 26093811