Skip to main content
Top
Published in: Cancer and Metastasis Reviews 2-3/2014

01-09-2014

A multi-targeted approach to treating bone metastases

Authors: Daniel F. Camacho, Kenneth J. Pienta

Published in: Cancer and Metastasis Reviews | Issue 2-3/2014

Login to get access

Abstract

The treatment of bone-metastatic cancer now takes advantage of the unique biology of this clinical state. The complex interplay between the cancer cells and the bone microenvironment leads to a host of therapeutic targets, with agents in various stages of clinical use or study. Targets include interactions between the cancer cells and osteoclasts, osteoblasts, endothelial cells, stromal cells, hematopoietic progenitor cells, cells of the immune system, and the bone matrix. Efforts at understanding specific mechanisms of drug resistance in the bone are also ongoing. Successful clinical outcomes will be the result of co-targeting and interrupting the various tumor-supportive elements and cooperating pathways at the level of the tumor cell, the primary and metastatic microenvironments, and systemic cancer effects, leading to a “scaled network disruption” to undermine the disease state.
Literature
1.
go back to reference Li, S., Peng, Y., Weinhandl, E. D., Blaes, A. H., Cetin, K., & Chia, V. M., et al. (2012). Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol, 4, 87–93. Li, S., Peng, Y., Weinhandl, E. D., Blaes, A. H., Cetin, K., & Chia, V. M., et al. (2012). Estimated number of prevalent cases of metastatic bone disease in the US adult population. Clin Epidemiol, 4, 87–93.
2.
go back to reference Loberg, R. D., Bradley, D. A., Tomlins, S. A., Chinnaiyan, A. M., & Pienta, K. J. (2007). The lethal phenotype of cancer: the molecular basis of death due to malignancy. CA: A Cancer Journal for Clinicians, 57(4), 225–241. Loberg, R. D., Bradley, D. A., Tomlins, S. A., Chinnaiyan, A. M., & Pienta, K. J. (2007). The lethal phenotype of cancer: the molecular basis of death due to malignancy. CA: A Cancer Journal for Clinicians, 57(4), 225–241.
3.
go back to reference Fidler, I. (2003). The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nature Reviews. Cancer, 3, 1–6.CrossRef Fidler, I. (2003). The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nature Reviews. Cancer, 3, 1–6.CrossRef
4.
go back to reference Paget, S. (1889). The distribution of secondary growth in cancer of breast. Lancet, 1, 98–101. Paget, S. (1889). The distribution of secondary growth in cancer of breast. Lancet, 1, 98–101.
5.
go back to reference Ewing, J. (1919). Metastasis. In Neoplastic diseases (pp. 76–88). Philadelphia: Saunders. Ewing, J. (1919). Metastasis. In Neoplastic diseases (pp. 76–88). Philadelphia: Saunders.
6.
go back to reference Pienta, K. J., & Loberg, R. (2005). The ‘emigration, migration, and immigration’ of prostate cancer. Clinical Prostate Cancer, 4(1), 24–30.PubMedCrossRef Pienta, K. J., & Loberg, R. (2005). The ‘emigration, migration, and immigration’ of prostate cancer. Clinical Prostate Cancer, 4(1), 24–30.PubMedCrossRef
7.
go back to reference Norton, L. (1988). A Gompertzian model of human breast cancer growth. Cancer Research, 48, 7067–7071.PubMed Norton, L. (1988). A Gompertzian model of human breast cancer growth. Cancer Research, 48, 7067–7071.PubMed
8.
9.
go back to reference Wang, J., Loberg, R., & Taichman, R. S. (2006). The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis. Cancer Metastasis Reviews, 25(4), 573–587.PubMedCrossRef Wang, J., Loberg, R., & Taichman, R. S. (2006). The pivotal role of CXCL12 (SDF-1)/CXCR4 axis in bone metastasis. Cancer Metastasis Reviews, 25(4), 573–587.PubMedCrossRef
10.
go back to reference Kortesidis, A., Zannettino, A., Isenmann, S., Shi, S., Lapidot, T., & Gronthos, S. (2005). Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood, 105(10), 3793–3801.PubMedCrossRef Kortesidis, A., Zannettino, A., Isenmann, S., Shi, S., Lapidot, T., & Gronthos, S. (2005). Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood, 105(10), 3793–3801.PubMedCrossRef
11.
go back to reference Jung, Y., Wang, J., Schneider, A., Sun, Y.-X., Koh-Paige, A. J., Osman, N. I., et al. (2006). Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone, 38(4), 497–508.PubMedCrossRef Jung, Y., Wang, J., Schneider, A., Sun, Y.-X., Koh-Paige, A. J., Osman, N. I., et al. (2006). Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone, 38(4), 497–508.PubMedCrossRef
12.
go back to reference Sun, Y., Fang, M., Wang, J., Cooper, C. R., Pienta, K. J., & Taichman, R. S., et al. (2007). Expression and Activation of a v b 3 Integrins by SDF-1 / CXC12 Increases the Aggressiveness of Prostate Cancer Cells. Prostate, 67(1), 61–73. Sun, Y., Fang, M., Wang, J., Cooper, C. R., Pienta, K. J., & Taichman, R. S., et al. (2007). Expression and Activation of a v b 3 Integrins by SDF-1 / CXC12 Increases the Aggressiveness of Prostate Cancer Cells. Prostate, 67(1), 61–73.
13.
go back to reference Sun, Y.-X., Schneider, A., Jung, Y., Wang, J., Dai, J., Wang, J., et al. (2005). Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. Journal of Bone and Mineral Research, 20(2), 318–329.PubMedCrossRef Sun, Y.-X., Schneider, A., Jung, Y., Wang, J., Dai, J., Wang, J., et al. (2005). Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. Journal of Bone and Mineral Research, 20(2), 318–329.PubMedCrossRef
14.
go back to reference Havens, A. M., Jung, Y., Sun, Y. X., Wang, J., Shah, R., Bühring, H., et al. (2006). The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis. BMC cancer, 6, 195.PubMedCentralPubMedCrossRef Havens, A. M., Jung, Y., Sun, Y. X., Wang, J., Shah, R., Bühring, H., et al. (2006). The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis. BMC cancer, 6, 195.PubMedCentralPubMedCrossRef
15.
go back to reference Jung, Y., Wang, J., Song, J., Shiozawa, Y., Wang, J., Havens, A., et al. (2007). Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood, 110(1), 82–90.PubMedCentralPubMedCrossRef Jung, Y., Wang, J., Song, J., Shiozawa, Y., Wang, J., Havens, A., et al. (2007). Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood, 110(1), 82–90.PubMedCentralPubMedCrossRef
16.
go back to reference Sikes, R. A., Nicholson, B. E., Koeneman, K. S., Edlund, N. M., Bissonette, E. A., Bradley, M. J., et al. (2004). Cellular interactions in the tropism of prostate cancer to bone. International Journal of Cancer, 110(4), 497–503.CrossRef Sikes, R. A., Nicholson, B. E., Koeneman, K. S., Edlund, N. M., Bissonette, E. A., Bradley, M. J., et al. (2004). Cellular interactions in the tropism of prostate cancer to bone. International Journal of Cancer, 110(4), 497–503.CrossRef
17.
go back to reference Chung, L. W. K., Baseman, A., Assikis, V., & Zhau, H. E. (2005). Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. The Journal of Urology, 173, 10–20.PubMedCrossRef Chung, L. W. K., Baseman, A., Assikis, V., & Zhau, H. E. (2005). Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. The Journal of Urology, 173, 10–20.PubMedCrossRef
18.
go back to reference Lipton, A. (2006). Future treatment of bone metastases. Clinical Cancer Research, 12(20 Pt 2), 6305s–6308s.PubMedCrossRef Lipton, A. (2006). Future treatment of bone metastases. Clinical Cancer Research, 12(20 Pt 2), 6305s–6308s.PubMedCrossRef
19.
go back to reference Mundy, G. R. (2002). Metastasis to bone: causes, consequences and therapeutic opportunities. Nature reviews. Cancer, 2(8), 584–593.PubMedCrossRef Mundy, G. R. (2002). Metastasis to bone: causes, consequences and therapeutic opportunities. Nature reviews. Cancer, 2(8), 584–593.PubMedCrossRef
20.
go back to reference Loberg, R. D., Logothetis, C. J., Keller, E. T., & Pienta, K. J. (2005). Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23(32), 8232–8241.CrossRef Loberg, R. D., Logothetis, C. J., Keller, E. T., & Pienta, K. J. (2005). Pathogenesis and treatment of prostate cancer bone metastases: targeting the lethal phenotype. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 23(32), 8232–8241.CrossRef
21.
go back to reference Candelaria-Quintana, D., Dayao, Z. R., & Royce, M. E. (2012). The role of antiresorptive therapies in improving patient care in early and metastatic breast cancer. Breast cancer research and treatment, 132(2), 355–363.PubMedCrossRef Candelaria-Quintana, D., Dayao, Z. R., & Royce, M. E. (2012). The role of antiresorptive therapies in improving patient care in early and metastatic breast cancer. Breast cancer research and treatment, 132(2), 355–363.PubMedCrossRef
22.
go back to reference Fornier, M. N. (2010). Denosumab: second chapter in controlling bone metastases or a new book? Journal of Clinical Oncology, 28(35), 5127–5131.PubMedCrossRef Fornier, M. N. (2010). Denosumab: second chapter in controlling bone metastases or a new book? Journal of Clinical Oncology, 28(35), 5127–5131.PubMedCrossRef
24.
go back to reference Wu, S., Dahut, W. L., & Gulley, J. L. (2007). The use of bisphosphonates in cancer patients. Acta Oncologica, 46(5), 581–591.PubMedCrossRef Wu, S., Dahut, W. L., & Gulley, J. L. (2007). The use of bisphosphonates in cancer patients. Acta Oncologica, 46(5), 581–591.PubMedCrossRef
25.
go back to reference Saad, F., Gleason, D. M., Murray, R., Tchekmedyian, S., Venner, P., Lacombe, L., et al. (2004). Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. Journal of the National Cancer Institute, 96(11), 879–882.PubMedCrossRef Saad, F., Gleason, D. M., Murray, R., Tchekmedyian, S., Venner, P., Lacombe, L., et al. (2004). Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. Journal of the National Cancer Institute, 96(11), 879–882.PubMedCrossRef
26.
go back to reference Lüftner, D., Henschke, P., & Possinger, K. (2007). Clinical value of bisphosphonates in cancer therapy. Anticancer research, 27(4A), 1759–1768.PubMed Lüftner, D., Henschke, P., & Possinger, K. (2007). Clinical value of bisphosphonates in cancer therapy. Anticancer research, 27(4A), 1759–1768.PubMed
27.
go back to reference Schwarz, E. M., & Ritchlin, C. T. (2007). Clinical development of anti-RANKL therapy. Arthritis Research & Therapy, 9(Suppl 1), S7.CrossRef Schwarz, E. M., & Ritchlin, C. T. (2007). Clinical development of anti-RANKL therapy. Arthritis Research & Therapy, 9(Suppl 1), S7.CrossRef
28.
go back to reference Tsourdi, E., Rachner, T. D., Rauner, M., Hamann, C., & Hofbauer, L. C. (2011). Denosumab for bone diseases: translating bone biology into targeted therapy. European Journal of Endocrinology, 165(6), 833–840.PubMedCrossRef Tsourdi, E., Rachner, T. D., Rauner, M., Hamann, C., & Hofbauer, L. C. (2011). Denosumab for bone diseases: translating bone biology into targeted therapy. European Journal of Endocrinology, 165(6), 833–840.PubMedCrossRef
29.
go back to reference Miyazaki, T., Tanaka, S., Sanjay, A., & Baron, R. (2006). The role of c-Src kinase in the regulation of osteoclast function. Modern Rheumatology, 16(2), 68–74.PubMedCrossRef Miyazaki, T., Tanaka, S., Sanjay, A., & Baron, R. (2006). The role of c-Src kinase in the regulation of osteoclast function. Modern Rheumatology, 16(2), 68–74.PubMedCrossRef
30.
go back to reference Huang, F., Reeves, K., Han, X., Fairchild, C., Platero, S., Wong, T. W., et al. (2007). Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer research, 67(5), 2226–2238.PubMedCrossRef Huang, F., Reeves, K., Han, X., Fairchild, C., Platero, S., Wong, T. W., et al. (2007). Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer research, 67(5), 2226–2238.PubMedCrossRef
31.
go back to reference Vandyke, K., Dewar, A. L., Diamond, P., Fitter, S., Schultz, C. G., Sims, N. A., et al. (2010). The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo. Journal of Bone and Mineral Research, 25(8), 1759–1770.PubMedCrossRef Vandyke, K., Dewar, A. L., Diamond, P., Fitter, S., Schultz, C. G., Sims, N. A., et al. (2010). The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo. Journal of Bone and Mineral Research, 25(8), 1759–1770.PubMedCrossRef
32.
go back to reference Ritchie, C. K., Andrews, L. R., Thomas, K. G., Tindall, D. J., & Fitzpatrick, L. A. (1997). The effects of growth factors associated with osteoblasts on prostate carcinoma proliferation and chemotaxis : implications for the development of metastatic disease. Endocrinology, 138(3), 1145–1150.PubMed Ritchie, C. K., Andrews, L. R., Thomas, K. G., Tindall, D. J., & Fitzpatrick, L. A. (1997). The effects of growth factors associated with osteoblasts on prostate carcinoma proliferation and chemotaxis : implications for the development of metastatic disease. Endocrinology, 138(3), 1145–1150.PubMed
33.
go back to reference Zangari, M., Esseltine, D., Lee, C.-K., Barlogie, B., Elice, F., Burns, M. J., et al. (2005). Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma. British Journal of Haematology, 131, 71–73.PubMedCrossRef Zangari, M., Esseltine, D., Lee, C.-K., Barlogie, B., Elice, F., Burns, M. J., et al. (2005). Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma. British Journal of Haematology, 131, 71–73.PubMedCrossRef
34.
go back to reference Terpos, E., Heath, D. J., Rahemtulla, A., Zervas, K., Chantry, A., Anagnostopoulos, A., et al. (2006). Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. British Journal of Haematology, 135(5), 688–692.PubMedCrossRef Terpos, E., Heath, D. J., Rahemtulla, A., Zervas, K., Chantry, A., Anagnostopoulos, A., et al. (2006). Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. British Journal of Haematology, 135(5), 688–692.PubMedCrossRef
35.
go back to reference Vessella, R. L., & Corey, E. (2006). Targeting factors involved in bone remodeling as treatment strategies in prostate cancer bone metastasis. Clinical Cancer Research, 12(20 Pt 2), 6285s–6290s.PubMedCrossRef Vessella, R. L., & Corey, E. (2006). Targeting factors involved in bone remodeling as treatment strategies in prostate cancer bone metastasis. Clinical Cancer Research, 12(20 Pt 2), 6285s–6290s.PubMedCrossRef
36.
go back to reference Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., & Anderson, K. C. (2005). Proteasome inhibitor therapy in multiple myeloma. Molecular Cancer Therapeutics, 4(4), 686–692.PubMedCrossRef Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., & Anderson, K. C. (2005). Proteasome inhibitor therapy in multiple myeloma. Molecular Cancer Therapeutics, 4(4), 686–692.PubMedCrossRef
37.
go back to reference Kane, R. C., Dagher, R., Farrell, A., Ko, C.-W., Sridhara, R., Justice, R., et al. (2007). Bortezomib for the treatment of mantle cell lymphoma. Clinical Cancer Research, 13(18 Pt 1), 5291–5294.PubMedCrossRef Kane, R. C., Dagher, R., Farrell, A., Ko, C.-W., Sridhara, R., Justice, R., et al. (2007). Bortezomib for the treatment of mantle cell lymphoma. Clinical Cancer Research, 13(18 Pt 1), 5291–5294.PubMedCrossRef
38.
go back to reference Sartor, O. (2004). Overview of samarium Sm 153 lexidronam in the treatment of painful metastatic bone disease. Reviews in Urology, 6(Suppl 10), S3–S12.PubMedCentralPubMed Sartor, O. (2004). Overview of samarium Sm 153 lexidronam in the treatment of painful metastatic bone disease. Reviews in Urology, 6(Suppl 10), S3–S12.PubMedCentralPubMed
39.
go back to reference Porter, A. T., McEwan, A. J., Powe, J. E., Reid, R., McGowan, D. G., Lukka, H., et al. (1993). Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int. J. Radiation Oncology Biol. Phys., 25, 805–813.CrossRef Porter, A. T., McEwan, A. J., Powe, J. E., Reid, R., McGowan, D. G., Lukka, H., et al. (1993). Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int. J. Radiation Oncology Biol. Phys., 25, 805–813.CrossRef
40.
go back to reference Baczyk, M., Czepczyński, R., Milecki, P., Pisarek, M., Oleksa, R., & Sowiński, J. (2007). 89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nuclear Medicine Communications, 28(4), 245–250.PubMedCrossRef Baczyk, M., Czepczyński, R., Milecki, P., Pisarek, M., Oleksa, R., & Sowiński, J. (2007). 89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nuclear Medicine Communications, 28(4), 245–250.PubMedCrossRef
41.
go back to reference Bauman, G., Charette, M., Reid, R., & Sathya, J. (2005). Radiopharmaceuticals for the palliation of painful bone metastases—a systematic review. Radiotherapy and Oncology, 75(3), 258. E1–258.E13.PubMedCrossRef Bauman, G., Charette, M., Reid, R., & Sathya, J. (2005). Radiopharmaceuticals for the palliation of painful bone metastases—a systematic review. Radiotherapy and Oncology, 75(3), 258. E1–258.E13.PubMedCrossRef
42.
go back to reference Akerley, W., Butera, J., Wehbe, T., Noto, R., Stein, B., Safran, H., et al. (2002). A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer, 94(6), 1654–1660.PubMedCrossRef Akerley, W., Butera, J., Wehbe, T., Noto, R., Stein, B., Safran, H., et al. (2002). A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone. Cancer, 94(6), 1654–1660.PubMedCrossRef
43.
go back to reference Tu, S. M., Millikan, R. E., Mengistu, B., Delpassand, E. S., Amato, R. J., Pagliaro, L. C., et al. (2001). Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet, 357, 336–341.PubMedCrossRef Tu, S. M., Millikan, R. E., Mengistu, B., Delpassand, E. S., Amato, R. J., Pagliaro, L. C., et al. (2001). Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet, 357, 336–341.PubMedCrossRef
44.
go back to reference Harrison, M. R., Wong, T. Z., Armstrong, A. J., & George, D. J. (2013). Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Management and Research, 5, 1–14.PubMedCentralPubMedCrossRef Harrison, M. R., Wong, T. Z., Armstrong, A. J., & George, D. J. (2013). Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Management and Research, 5, 1–14.PubMedCentralPubMedCrossRef
45.
go back to reference Rao, K. V. (2007). Lenalidomide in the treatment of multiple myeloma. American Journal of Health-System Pharmacy, 64(17), 1799–1807.PubMedCrossRef Rao, K. V. (2007). Lenalidomide in the treatment of multiple myeloma. American Journal of Health-System Pharmacy, 64(17), 1799–1807.PubMedCrossRef
46.
go back to reference Murakami, H., Handa, H., Abe, M., Iida, S., Ishii, A., Ishikawa, T., et al. (2007). Low-dose thalidomide plus low-dose dexamethasone therapy in patients with refractory multiple myeloma. European Journal of Haematology, 79(3), 234–239.PubMedCrossRef Murakami, H., Handa, H., Abe, M., Iida, S., Ishii, A., Ishikawa, T., et al. (2007). Low-dose thalidomide plus low-dose dexamethasone therapy in patients with refractory multiple myeloma. European Journal of Haematology, 79(3), 234–239.PubMedCrossRef
47.
go back to reference Hicklin, D. J., & Ellis, L. M. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of Clinical Oncology, 23(5), 1011–1027.PubMedCrossRef Hicklin, D. J., & Ellis, L. M. (2005). Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. Journal of Clinical Oncology, 23(5), 1011–1027.PubMedCrossRef
48.
go back to reference Chinot, O. L. (2012). Bevacizumab-based therapy in relapsed glioblastoma: rationale and clinical experience to date. Expert Review of Anticancer Therapy, 12(11), 1413–1427.PubMedCrossRef Chinot, O. L. (2012). Bevacizumab-based therapy in relapsed glioblastoma: rationale and clinical experience to date. Expert Review of Anticancer Therapy, 12(11), 1413–1427.PubMedCrossRef
49.
go back to reference Flaherty, K. T. (2007). Sorafenib: delivering a targeted drug to the right targets. Expert Review of Anticancer Therapy, 7(5), 617–626.PubMedCrossRef Flaherty, K. T. (2007). Sorafenib: delivering a targeted drug to the right targets. Expert Review of Anticancer Therapy, 7(5), 617–626.PubMedCrossRef
50.
go back to reference Pantuck, A. J., Zomorodian, N., & Belldegrun, A. S. (2006). Phase I, open-label, single-center, multiple-dose, dose-escalation clinical study of SUO11248 (sunitinib) in subjects with high-risk prostate cancer who have elected to undergo radical prostatectomy. Clinical Cancer Research, 12, 4018–4026.PubMedCrossRef Pantuck, A. J., Zomorodian, N., & Belldegrun, A. S. (2006). Phase I, open-label, single-center, multiple-dose, dose-escalation clinical study of SUO11248 (sunitinib) in subjects with high-risk prostate cancer who have elected to undergo radical prostatectomy. Clinical Cancer Research, 12, 4018–4026.PubMedCrossRef
51.
go back to reference Drevs, J., Zirrgiebel, U., Schmidt-Gersbach, C. I. M., Mross, K., Medinger, M., Lee, L., et al. (2005). Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials. Annals of Oncology, 16(4), 558–565.PubMedCrossRef Drevs, J., Zirrgiebel, U., Schmidt-Gersbach, C. I. M., Mross, K., Medinger, M., Lee, L., et al. (2005). Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials. Annals of Oncology, 16(4), 558–565.PubMedCrossRef
52.
go back to reference Smith, D. C., Smith, M. R., Sweeney, C., Elfiky, A. A., Logothetis, C., Corn, P. G., et al. (2013). Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. Journal of Clinical Oncology, 31(4), 412–419.PubMedCrossRef Smith, D. C., Smith, M. R., Sweeney, C., Elfiky, A. A., Logothetis, C., Corn, P. G., et al. (2013). Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. Journal of Clinical Oncology, 31(4), 412–419.PubMedCrossRef
53.
go back to reference Eskens, F. A. L. M., Dumez, H., Hoekstra, R., Perschl, A., Brindley, C., Böttcher, S., et al. (2003). Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours. European Journal of Cancer, 39(7), 917–926.PubMedCrossRef Eskens, F. A. L. M., Dumez, H., Hoekstra, R., Perschl, A., Brindley, C., Böttcher, S., et al. (2003). Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours. European Journal of Cancer, 39(7), 917–926.PubMedCrossRef
54.
go back to reference Mullamitha, S. A., Ton, N. C., Parker, G. J. M., Jackson, A., Julyan, P. J., Roberts, C., et al. (2007). Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clinical Cancer Research, 13(7), 2128–2135.PubMedCrossRef Mullamitha, S. A., Ton, N. C., Parker, G. J. M., Jackson, A., Julyan, P. J., Roberts, C., et al. (2007). Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (CNTO 95) in patients with advanced solid tumors. Clinical Cancer Research, 13(7), 2128–2135.PubMedCrossRef
55.
go back to reference Tucker, G. C. (2006). Integrins: molecular targets in cancer therapy. Current Oncology Reports, 8(2), 96–103.PubMedCrossRef Tucker, G. C. (2006). Integrins: molecular targets in cancer therapy. Current Oncology Reports, 8(2), 96–103.PubMedCrossRef
56.
go back to reference Gramoun, A., Shorey, S., Bashutski, J. D., Dixon, S. J., Sims, S. M., Heersche, J. N. M., et al. (2007). Effects of vitaxin, a novel therapeutic in trial for metastatic bone tumors, on osteoclast functions in vitro. Journal of Cellular Biochemistry, 102(2), 341–352.PubMedCrossRef Gramoun, A., Shorey, S., Bashutski, J. D., Dixon, S. J., Sims, S. M., Heersche, J. N. M., et al. (2007). Effects of vitaxin, a novel therapeutic in trial for metastatic bone tumors, on osteoclast functions in vitro. Journal of Cellular Biochemistry, 102(2), 341–352.PubMedCrossRef
57.
go back to reference Mulgrew, K., Kinneer, K., Yao, X.-T., Ward, B. K., Damschroder, M. M., Walsh, B., et al. (2006). Direct targeting of alphavbeta3 integrin on tumor cells with a monoclonal antibody, Abegrin. Molecular Cancer Therapeutics, 5(12), 3122–3129.PubMedCrossRef Mulgrew, K., Kinneer, K., Yao, X.-T., Ward, B. K., Damschroder, M. M., Walsh, B., et al. (2006). Direct targeting of alphavbeta3 integrin on tumor cells with a monoclonal antibody, Abegrin. Molecular Cancer Therapeutics, 5(12), 3122–3129.PubMedCrossRef
58.
go back to reference Cheever, M. A., & Higano, C. S. (2011). PROVENGE (sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clinical Cancer Research, 17(11), 3520–3526.PubMedCrossRef Cheever, M. A., & Higano, C. S. (2011). PROVENGE (sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clinical Cancer Research, 17(11), 3520–3526.PubMedCrossRef
59.
go back to reference Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., et al. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine, 363(5), 411–422.PubMedCrossRef Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., et al. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine, 363(5), 411–422.PubMedCrossRef
60.
go back to reference So-Rosillo, R., & Small, E. J. (2006). Sipuleucel-T (APC8015) for prostate cancer. Expert Review of Anticancer Therapy, 6(9), 1163–1167.PubMedCrossRef So-Rosillo, R., & Small, E. J. (2006). Sipuleucel-T (APC8015) for prostate cancer. Expert Review of Anticancer Therapy, 6(9), 1163–1167.PubMedCrossRef
61.
go back to reference Park, J. W., Melisko, M. E., Esserman, L. J., Jones, L. A., Wollan, J. B., & Sims, R. (2007). Treatment with autologous antigen-presenting cells activated with the HER-2-based antigen lapuleucel-T: results of a phase I study in immunologic and clinical activity in HER-2 overexpressing breast cancer. Journal of Clinical Oncology, 25(24), 3680–3687.PubMedCrossRef Park, J. W., Melisko, M. E., Esserman, L. J., Jones, L. A., Wollan, J. B., & Sims, R. (2007). Treatment with autologous antigen-presenting cells activated with the HER-2-based antigen lapuleucel-T: results of a phase I study in immunologic and clinical activity in HER-2 overexpressing breast cancer. Journal of Clinical Oncology, 25(24), 3680–3687.PubMedCrossRef
62.
go back to reference de Gruijl, T. D., van den Eertwegh, A. J. M., Pinedo, H. M., & Scheper, R. J. (2008). Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunology, Immunotherapy, 57(10), 1569–1577.PubMedCentralPubMedCrossRef de Gruijl, T. D., van den Eertwegh, A. J. M., Pinedo, H. M., & Scheper, R. J. (2008). Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunology, Immunotherapy, 57(10), 1569–1577.PubMedCentralPubMedCrossRef
63.
go back to reference Kantoff, P. W., Schuetz, T. J., Blumenstein, B. A., Glode, L. M., Bilhartz, D. L., Wyand, M., et al. (2010). Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 28(7), 1099–1105.PubMedCentralPubMedCrossRef Kantoff, P. W., Schuetz, T. J., Blumenstein, B. A., Glode, L. M., Bilhartz, D. L., Wyand, M., et al. (2010). Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 28(7), 1099–1105.PubMedCentralPubMedCrossRef
64.
go back to reference Dayyani, F., Gallick, G. E., Logothetis, C. J., & Corn, P. G. (2011). Novel therapies for metastatic castrate-resistant prostate cancer. Journal of the National Cancer Institute, 103(22), 1665–1675.PubMedCrossRef Dayyani, F., Gallick, G. E., Logothetis, C. J., & Corn, P. G. (2011). Novel therapies for metastatic castrate-resistant prostate cancer. Journal of the National Cancer Institute, 103(22), 1665–1675.PubMedCrossRef
65.
go back to reference Reck, M., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al. (2013). Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Annals of Oncology, 24(1), 75–83.PubMedCrossRef Reck, M., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al. (2013). Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Annals of Oncology, 24(1), 75–83.PubMedCrossRef
66.
go back to reference Margolin, K., Ernstoff, M. S., Hamid, O., Lawrence, D., McDermott, D., Puzanov, I., et al. (2012). Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. The Lancet Oncology, 13(5), 459–465.PubMedCrossRef Margolin, K., Ernstoff, M. S., Hamid, O., Lawrence, D., McDermott, D., Puzanov, I., et al. (2012). Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. The Lancet Oncology, 13(5), 459–465.PubMedCrossRef
67.
go back to reference Sun, J., Schiffman, J., Raghunath, A., Ng Tang, D., Chen, H., & Sharma, P. (2008). Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy. Cancer Immunity, 8, 9–15.PubMedCentralPubMed Sun, J., Schiffman, J., Raghunath, A., Ng Tang, D., Chen, H., & Sharma, P. (2008). Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy. Cancer Immunity, 8, 9–15.PubMedCentralPubMed
68.
go back to reference Fulton, A., Miller, F., Weise, A., & Wei, W.-Z. (2007). Prospects of controlling breast cancer metastasis by immune intervention. Breast Disease, 26, 115–127. Fulton, A., Miller, F., Weise, A., & Wei, W.-Z. (2007). Prospects of controlling breast cancer metastasis by immune intervention. Breast Disease, 26, 115–127.
69.
go back to reference Melero, I., Grimaldi, A. M., Perez-Gracia, J. L., & Ascierto, P. A. (2013). Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clinical cancer research : an official journal of the American Association for Cancer Research, 19(5), 997–1008.CrossRef Melero, I., Grimaldi, A. M., Perez-Gracia, J. L., & Ascierto, P. A. (2013). Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clinical cancer research : an official journal of the American Association for Cancer Research, 19(5), 997–1008.CrossRef
70.
go back to reference Fishelson, Z., Donin, N., Zell, S., Schultz, S., & Kirschfink, M. (2003). Obstacles to cancer immunotherapy: expression of membrane complement regulatory proteins (mCRPs) in tumors. Molecular Immunology, 40, 109–123.PubMedCrossRef Fishelson, Z., Donin, N., Zell, S., Schultz, S., & Kirschfink, M. (2003). Obstacles to cancer immunotherapy: expression of membrane complement regulatory proteins (mCRPs) in tumors. Molecular Immunology, 40, 109–123.PubMedCrossRef
71.
go back to reference Pritchard-Jones, K., Spendlove, I., Wilton, C., Whelan, J., Weeden, S., Lewis, I., et al. (2005). Immune responses to the 105 AD7 human anti-idiotypic vaccine after intensive chemotherapy, for osteosarcoma. British Journal of Cancer, 92(8), 1358–1365.PubMedCentralPubMedCrossRef Pritchard-Jones, K., Spendlove, I., Wilton, C., Whelan, J., Weeden, S., Lewis, I., et al. (2005). Immune responses to the 105 AD7 human anti-idiotypic vaccine after intensive chemotherapy, for osteosarcoma. British Journal of Cancer, 92(8), 1358–1365.PubMedCentralPubMedCrossRef
72.
go back to reference Liao, Y., Schaue, D., & McBride, W. (2007). Modification of the tumor microenvironment to enhance immunity. Frontiers in Bioscience, 12, 3576–3600.PubMedCrossRef Liao, Y., Schaue, D., & McBride, W. (2007). Modification of the tumor microenvironment to enhance immunity. Frontiers in Bioscience, 12, 3576–3600.PubMedCrossRef
73.
go back to reference Dirkx, A. E. M., Oude Egbrink, M. G. A., Wagstaff, J., & Griffioen, A. W. (2006). Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Journal of Leukocyte Biology, 80(6), 1183–1196.PubMedCrossRef Dirkx, A. E. M., Oude Egbrink, M. G. A., Wagstaff, J., & Griffioen, A. W. (2006). Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. Journal of Leukocyte Biology, 80(6), 1183–1196.PubMedCrossRef
74.
go back to reference Lewis, C. E., & Pollard, J. W. (2006). Distinct role of macrophages in different tumor microenvironments. Cancer Research, 66(2), 605–612.PubMedCrossRef Lewis, C. E., & Pollard, J. W. (2006). Distinct role of macrophages in different tumor microenvironments. Cancer Research, 66(2), 605–612.PubMedCrossRef
75.
go back to reference Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. Journal of Pathology, 196, 254–265.PubMedCrossRef Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. Journal of Pathology, 196, 254–265.PubMedCrossRef
76.
go back to reference Sica, A., Schioppa, T., Mantovani, A., & Allavena, P. (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. European Journal of Cancer, 42(6), 717–727.PubMedCrossRef Sica, A., Schioppa, T., Mantovani, A., & Allavena, P. (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. European Journal of Cancer, 42(6), 717–727.PubMedCrossRef
77.
go back to reference Mantovani, A., Schioppa, T., Porta, C., Allavena, P., & Sica, A. (2006). Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Reviews, 25(3), 315–322.PubMedCrossRef Mantovani, A., Schioppa, T., Porta, C., Allavena, P., & Sica, A. (2006). Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Reviews, 25(3), 315–322.PubMedCrossRef
78.
go back to reference Porta, C., Kumar, B. S., Larghi, P., Rubino, L., Mancino, A., & Sica, A. (2007). Tumor promotion by tumor-associated macrophages. Advances in Experimental Medicine and Biology, 604, 67–86.PubMedCrossRef Porta, C., Kumar, B. S., Larghi, P., Rubino, L., Mancino, A., & Sica, A. (2007). Tumor promotion by tumor-associated macrophages. Advances in Experimental Medicine and Biology, 604, 67–86.PubMedCrossRef
79.
go back to reference Loberg, R. D., Ying, C., Craig, M., Yan, L., Snyder, L. A., & Pienta, K. J. (2007). CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia, 9(7), 556–562.PubMedCentralPubMedCrossRef Loberg, R. D., Ying, C., Craig, M., Yan, L., Snyder, L. A., & Pienta, K. J. (2007). CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia, 9(7), 556–562.PubMedCentralPubMedCrossRef
80.
go back to reference Bailey, C., Negus, R., Morris, A., Ziprin, P., Goldin, R., Allavena, P., et al. (2007). Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clinical & Experimental Metastasis, 24(2), 121–130.CrossRef Bailey, C., Negus, R., Morris, A., Ziprin, P., Goldin, R., Allavena, P., et al. (2007). Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clinical & Experimental Metastasis, 24(2), 121–130.CrossRef
81.
go back to reference Craig, M. J., & Loberg, R. D. (2006). CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases. Cancer Metastasis Reviews, 25(4), 611–619.PubMedCrossRef Craig, M. J., & Loberg, R. D. (2006). CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases. Cancer Metastasis Reviews, 25(4), 611–619.PubMedCrossRef
82.
go back to reference Pienta, K. J., Machiels, J.-P., Schrijvers D., Alekseev B., M. Shkolnik, & Crabb, S. J., et al. (2013). Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs, 31(3), 760–768. Pienta, K. J., Machiels, J.-P., Schrijvers D., Alekseev B., M. Shkolnik, & Crabb, S. J., et al. (2013). Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Invest New Drugs, 31(3), 760–768.
83.
go back to reference Sandhu, S. K., Papadopoulos, K., Fong, P. C., Patnaik, A., Messiou, C., Olmos, D., et al. (2013). A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemotherapy and Pharmacology, 71(4), 1041–1050.PubMedCrossRef Sandhu, S. K., Papadopoulos, K., Fong, P. C., Patnaik, A., Messiou, C., Olmos, D., et al. (2013). A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemotherapy and Pharmacology, 71(4), 1041–1050.PubMedCrossRef
84.
go back to reference Baay, M., Brouwer, A., Pauwels, P., Peeters, M., & Lardon, F. (2011). Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy. Clinical & Developmental Immunology, p. 565187. Baay, M., Brouwer, A., Pauwels, P., Peeters, M., & Lardon, F. (2011). Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy. Clinical & Developmental Immunology, p. 565187.
85.
go back to reference Petit, I., Szyper-Kravitz, M., Nagler, A., Lahav, M., Peled, A., Habler, L., et al. (2002). G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunology, 3(7), 687–694.PubMedCrossRef Petit, I., Szyper-Kravitz, M., Nagler, A., Lahav, M., Peled, A., Habler, L., et al. (2002). G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunology, 3(7), 687–694.PubMedCrossRef
86.
go back to reference Shiozawa, Y., Pedersen, E. A., Havens, A. M., Jung, Y., Mishra, A., Joseph, J., et al. (2011). Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. Journal of Clinical Investigation, 121(4), 1298–1312.PubMedCentralPubMedCrossRef Shiozawa, Y., Pedersen, E. A., Havens, A. M., Jung, Y., Mishra, A., Joseph, J., et al. (2011). Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. Journal of Clinical Investigation, 121(4), 1298–1312.PubMedCentralPubMedCrossRef
87.
go back to reference Smith, M. C. P., Luker, K. E., Garbow, J. R., Prior, J. L., Jackson, E., Piwnica-Worms, D., et al. (2004). CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Research, 64(23), 8604–8612.PubMedCrossRef Smith, M. C. P., Luker, K. E., Garbow, J. R., Prior, J. L., Jackson, E., Piwnica-Worms, D., et al. (2004). CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Research, 64(23), 8604–8612.PubMedCrossRef
88.
go back to reference Meads, M. B., Hazlehurst, L. A., & Dalton, W. S. (2008). The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clinical Cancer Research, 14(9), 2519–2526.PubMedCrossRef Meads, M. B., Hazlehurst, L. A., & Dalton, W. S. (2008). The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clinical Cancer Research, 14(9), 2519–2526.PubMedCrossRef
89.
go back to reference Vincent, T., & Mechti, N. (2005). Extracellular matrix in bone marrow can mediate drug resistance in myeloma. Leukemia & Lymphoma, 46(6), 803–811.CrossRef Vincent, T., & Mechti, N. (2005). Extracellular matrix in bone marrow can mediate drug resistance in myeloma. Leukemia & Lymphoma, 46(6), 803–811.CrossRef
90.
go back to reference Camacho, D. F., & Pienta, K. J. (2012). Disrupting the networks of cancer. Clinical Cancer Research, 18(10), 2801–2808.PubMedCrossRef Camacho, D. F., & Pienta, K. J. (2012). Disrupting the networks of cancer. Clinical Cancer Research, 18(10), 2801–2808.PubMedCrossRef
91.
go back to reference Chen, K. W., & Pienta, K. J. (2011). Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles. Theoretical Biology and Medical Modeling, 8(36), 1–11. Chen, K. W., & Pienta, K. J. (2011). Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles. Theoretical Biology and Medical Modeling, 8(36), 1–11.
Metadata
Title
A multi-targeted approach to treating bone metastases
Authors
Daniel F. Camacho
Kenneth J. Pienta
Publication date
01-09-2014
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 2-3/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-013-9476-y

Other articles of this Issue 2-3/2014

Cancer and Metastasis Reviews 2-3/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine