Bone Metastasis: Current State of Play

Anthony Turpin, Martine Duterque-Coquillaud, Marie-Hélène Vieillard, Anthony Turpin, Martine Duterque-Coquillaud, Marie-Hélène Vieillard

Abstract

Bone metastasis (BM) in cancer remains a critical issue because of its associated clinical and biological complications. Moreover, BM can alter the quality of life and survival rate of cancer patients. Growing evidence suggests that bones are a fertile ground for the development of metastasis through a "vicious circle" of bone resorption/formation and tumor growth. This review aims to outline the current major issues in the diagnosis and management of BM in the most common types of osteotropic cancers and describe the mechanisms and effects of BM. First, we discuss the incidence of BM through the following questions: Are we witnessing an increase in incidence, and are we now better equipped with modern imaging techniques? Is the advent of efficient bone resorption inhibitors affecting the bigger picture of BM management? Second, we discuss the potential effects of cancer progression and well-prescribed drugs, such as multitarget tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, and immune checkpoint inhibitors, on BM. Finally, we examine the duality of the effects of some therapies that may help in cancer treatment but may also contribute to further BM.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Targeted therapies and their potential effects on bone remodeling and suggested contribution to bone carcinogenesis and resistance to treatment. Targeted therapies have improved the outcomes of patients with osteotropic cancers, but the reactivation of different pathways can induce bone disorders and contribute to resistance to treatment. This remodeling of the tumor, bone microenvironment, and immunity may participate in clonal selection of metastases, both in the bone—by reactivating a “vicious circle” promoting bone homing—and in other organs. bFGF: basic fibroblast growth factor, BMP: bone marrow protein, DKK-1: Dickkopf-related protein 1, ET-1: endothelin-1, HGF: hepatocyte growth factor, IGF: insulin growth factor, IL: interleukin, IFNγ: interferon-gamma, M-CSF: monocyte-colony stimulating factor, MDSC: myeloid-derived suppressor cells, MMP-9: matrix metalloproteinase 9, NO: nitric oxide, NK: natural killer cell, PEG2: prostaglandin E2, PDGF: platelet-derived growth factor, PTHrP: parathormone-related protein, RANK: receptor activator of nuclear factor kappa-B, RANKL: receptor activator of nuclear factor kappa-B ligand, SOST: sclerostin, TAM: tumor-associated macrophages, TAN: tumor-associated neutrophils, TGF: transforming growth factor, TNFα: tumor necrosis factor-alpha, Treg: regulatory T cells, VEGF: vascular endothelial growth factor. Arrows in red (+): activation process. Arrows in blue (−): inhibition process.

References

    1. Roodman G.D. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655–1664.
    1. Coleman R.E. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s–6249s.
    1. Fornetti J., Welm A.L., Stewart S.A. Understanding the Bone in Cancer Metastasis. J Bone Miner Res. 2018;33:2099–2113.
    1. Selvaggi G., Scagliotti G.V. Management of bone metastases in cancer: a review. Crit Rev Oncol Hematol. 2005;56:365–378.
    1. Coleman R.E. Bisphosphonates: clinical experience. Oncologist. 2004;9(Suppl 4):14–27.
    1. McDougall J.A., Bansal A., Goulart B.H.L., McCune J.S., Karnopp A., Fedorenko C., Greenlee S., Valderrama A., Sullivan S.D., Ramsey S.D. The Clinical and Economic Impacts of Skeletal-Related Events Among Medicare Enrollees With Prostate Cancer Metastatic to Bone. Oncologist. 2016;21:320–326.
    1. Lecouvet F.E., Oprea-Lager D.E., Liu Y., Ost P., Bidaut L., Collette L., Deroose C.M., Goffin K., Herrmann K., Hoekstra O.S. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group. Lancet Oncol. 2018;19:e534–e545.
    1. Massagué J., Obenauf A.C. Metastatic colonization by circulating tumour cells. Nature. 2016;529:298–306.
    1. Body J.-J., Quinn G., Talbot S., Booth E., Demonty G., Taylor A., Amelio J. Systematic review and meta-analysis on the proportion of patients with breast cancer who develop bone metastases. Crit Rev Oncol/Hematol. 2017;115:67–80.
    1. Coleman R.E., Rubens R.D. The clinical course of bone metastases from breast cancer. Br J Cancer. 1987;55:61–66.
    1. Kuchuk I., Hutton B., Moretto P., Ng T., Addison C.L., Clemons M. Incidence, consequences and treatment of bone metastases in breast cancer patients-Experience from a single cancer centre. J Bone Oncol. 2013;2:137–144.
    1. Swain S.M., Baselga J., Kim S.-B., Ro J., Semiglazov V., Campone M., Ciruelos E., Ferrero J.-M., Schneeweiss A., Heeson S. Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2015;372:724–734.
    1. Diéras V., Miles D., Verma S., Pegram M., Welslau M., Baselga J., Krop I.E., Blackwell K., Hoersch S., Xu J. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:732–742.
    1. Cortes J., O’Shaughnessy J., Loesch D., Blum J.L., Vahdat L.T., Petrakova K., Chollet P., Manikas A., Diéras V., Delozier T. Twelves, EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389) investigators, Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914–923.
    1. Finn R.S., Crown J.P., Lang I., Boer K., Bondarenko I.M., Kulyk S.O., Ettl J., Patel R., Pinter T., Schmidt M. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16:25–35.
    1. Finn R.S., Martin M., Rugo H.S., Jones S., Im S.-A., Gelmon K., Harbeck N., Lipatov O.N., Walshe J.M., Moulder S. Palbociclib and Letrozole in Advanced Breast Cancer. New Engl J Med. 2016;375:1925–1936.
    1. Cristofanilli M., Turner N.C., Bondarenko I., Ro J., Im S.-A., Masuda N., Colleoni M., DeMichele A., Loi S., Verma S. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17:425–439.
    1. Baselga J., Campone M., Piccart M., Burris H.A., Rugo H.S., Sahmoud T., Noguchi S., Gnant M., Pritchard K.I., Lebrun F. Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer. N Engl J Med. 2012;366:520–529.
    1. Robson M., Im S.-A., Senkus E., Xu B., Domchek S.M., Masuda N., Delaloge S., Li W., Tung N., Armstrong A. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377:523–533.
    1. Gravis G., Fizazi K., Joly F., Oudard S., Priou F., Esterni B., Latorzeff I., Delva R., Krakowski I., Laguerre B. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:149–158.
    1. James N.D., Sydes M.R., Clarke N.W., Mason M.D., Dearnaley D.P., Spears M.R., Ritchie A.W.S., Parker C.C., Russell J.M., Attard G. STAMPEDE investigators, Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–1177.
    1. Sweeney C.J., Chen Y.-H., Carducci M., Liu G., Jarrard D.F., Eisenberger M., Wong Y.-N., Hahn N., Kohli M., Cooney M.M. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373:737–746.
    1. Fizazi K., Tran N., Fein L., Matsubara N., Rodriguez-Antolin A., Alekseev B.Y., Özgüroğlu M., Ye D., Feyerabend S., Protheroe A. LATITUDE Investigators, Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377:352–360.
    1. Ryan C.J., Smith M.R., Fizazi K., Saad F., Mulders P.F.A., Sternberg C.N., Miller K., Logothetis C.J., Shore N.D., Small E.J. COU-AA-302 Investigators, Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–160.
    1. Oudard S., Fizazi K., Sengeløv L., Daugaard G., Saad F., Hansen S., Hjälm-Eriksson M., Jassem J., Thiery-Vuillemin A., Caffo O. Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA. J Clin Oncol. 2017;35:3189–3197.
    1. Fizazi K., Scher H.I., Molina A., Logothetis C.J., Chi K.N., Jones R.J., Staffurth J.N., North S., Vogelzang N.J., Saad F. COU-AA-301 Investigators, Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–992.
    1. Scher H.I., Fizazi K., Saad F., Taplin M.-E., Sternberg C.N., Miller K., de Wit R., Mulders P., Chi K.N., Shore N.D. AFFIRM Investigators, Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–1197.
    1. de Bono J.S., Oudard S., Ozguroglu M., Hansen S., Machiels J.-P., Kocak I., Gravis G., Bodrogi I., Mackenzie M.J., Shen L. TROPIC Investigators, Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–1154.
    1. Kuchuk M., Addison C.L., Clemons M., Kuchuk I., Wheatley-Price P. Incidence and consequences of bone metastases in lung cancer patients. J Bone Oncol. 2013;2:22–29.
    1. Wang H., Zhang Y., Zhu H., Yu J. Risk factors for bone metastasis in completely resected non-small-cell lung cancer. Future Oncol. 2017;13:695–704.
    1. Maemondo M., Inoue A., Kobayashi K., Sugawara S., Oizumi S., Isobe H., Gemma A., Harada M., Yoshizawa H., Kinoshita I. North-East Japan Study Group, Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362:2380–2388.
    1. Mok T.S., Wu Y.-L., Thongprasert S., Yang C.-H., Chu D.-T., Saijo N., Sunpaweravong P., Han B., Margono B., Ichinose Y. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–957.
    1. Solomon B.J., Mok T., Kim D.-W., Wu Y.-L., Nakagawa K., Mekhail T., Felip E., Cappuzzo F., Paolini J., Usari T. PROFILE 1014 Investigators, First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–2177.
    1. Hida T., Nokihara H., Kondo M., Kim Y.H., Azuma K., Seto T., Takiguchi Y., Nishio M., Yoshioka H., Imamura F. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390:29–39.
    1. Soria J.-C., Ohe Y., Vansteenkiste J., Reungwetwattana T., Chewaskulyong B., Lee K.H., Dechaphunkul A., Imamura F., Nogami N., Kurata T. FLAURA Investigators, Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:113–125.
    1. Rosell R., Carcereny E., Gervais R., Vergnenegre A., Massuti B., Felip E., Palmero R., Garcia-Gomez R., Pallares C., Sanchez J.M. Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica, Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–246.
    1. Shaw A.T., Kim D.-W., Nakagawa K., Seto T., Crinó L., Ahn M.-J., De Pas T., Besse B., Solomon B.J., Blackhall F. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–2394.
    1. Barlesi F., Scherpereel A., Rittmeyer A., Pazzola A., Ferrer Tur N., Kim J.-H., Ahn M.-J., Aerts J.G.J.V., Gorbunova V., Vikström A. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089) J Clin Oncol. 2013;31:3004–3011.
    1. Paz-Ares L., de Marinis F., Dediu M., Thomas M., Pujol J.-L., Bidoli P., Molinier O., Sahoo T.P., Laack E., Reck M. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012;13:247–255.
    1. Brahmer J., Reckamp K.L., Baas P., Crinò L., Eberhardt W.E.E., Poddubskaya E., Antonia S., Pluzanski A., Vokes E.E., Holgado E. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:123–135.
    1. Borghaei H., Paz-Ares L., Horn L., Spigel D.R., Steins M., Ready N.E., Chow L.Q., Vokes E.E., Felip E., Holgado E. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:1627–1639.
    1. Herbst R.S., Baas P., Kim D.-W., Felip E., Pérez-Gracia J.L., Han J.-Y., Molina J., Kim J.-H., Arvis C.D., Ahn M.-J. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–1550.
    1. Rittmeyer A., Barlesi F., Waterkamp D., Park K., Ciardiello F., von Pawel J., Gadgeel S.M., Hida T., Kowalski D.M., Dols M.C. OAK Study Group, Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255–265.
    1. Charpidou A., Tsagouli S., Gkiozos I., Grapsa D., Moutsos M., Kiagia M., Syrigos K. Bone metastases in patients with small cell lung carcinoma: rate of development, early versus late onset, modality of treatment, and their impact on survival. A single-institution retrospective cohort study. Clin Exp Metastasis. 2016;33:453–460.
    1. Bianchi M., Sun M., Jeldres C., Shariat S.F., Trinh Q.-D., Briganti A., Tian Z., Schmitges J., Graefen M., Perrotte P. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol. 2012;23:973–980.
    1. Motzer R.J., Hutson T.E., Cella D., Reeves J., Hawkins R., Guo J., Nathan P., Staehler M., de Souza P., Merchan J.R. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369:722–731.
    1. Choueiri T.K., Escudier B., Powles T., Tannir N.M., Mainwaring P.N., Rini B.I., Hammers H.J., Donskov F., Roth B.J., Peltola K. METEOR investigators, Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:917–927.
    1. Motzer R.J., Porta C., Vogelzang N.J., Sternberg C.N., Szczylik C., Zolnierek J., Kollmannsberger C., Rha S.Y., Bjarnason G.A., Melichar B. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:286–296.
    1. Escudier B., Porta C., Bono P., Powles T., Eisen T., Sternberg C.N., Gschwend J.E., De Giorgi U., Parikh O., Hawkins R. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014;32:1412–1418.
    1. Rini B.I., Escudier B., Tomczak P., Kaprin A., Szczylik C., Hutson T.E., Michaelson M.D., Gorbunova V.A., Gore M.E., Rusakov I.G. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378:1931–1939.
    1. Motzer R.J., Escudier B., McDermott D.F., George S., Hammers H.J., Srinivas S., Tykodi S.S., Sosman J.A., Procopio G., Plimack E.R. CheckMate 025 Investigators, Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373:1803–1813.
    1. Hussain A., Lee R.J., Graff J.N., Halabi S. The evolution and understanding of skeletal complication endpoints in clinical trials of tumors with metastasis to the bone. Crit Rev Oncol Hematol. 2019;139:108–116.
    1. Lipton A., Theriault R.L., Hortobagyi G.N., Simeone J., Knight R.D., Mellars K., Reitsma D.J., Heffernan M., Seaman J.J. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer. 2000;88:1082–1090.
    1. Saad F., Gleason D.M., Murray R., Tchekmedyian S., Venner P., Lacombe L., Chin J.L., Vinholes J.J., Goas J.A., Zheng M. Zoledronic Acid Prostate Cancer Study Group, Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96:879–882.
    1. Rosen L.S., Gordon D., Tchekmedyian N.S., Yanagihara R., Hirsh V., Krzakowski M., Pawlicki M., De Souza P., Zheng M., Urbanowitz G. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 2004;100:2613–2621.
    1. Yong M., Jensen A.Ö., Jacobsen J.B., Nørgaard M., Fryzek J.P., Sørensen H.T. Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark (1999-2007) Breast Cancer Res Treat. 2011;129:495–503.
    1. O’Sullivan G.J. Imaging of bone metastasis: An update. WJR. 2015;7:202.
    1. D’Oronzo S., Coleman R., Brown J., Silvestris F. Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management. J Bone Oncol. 2019;15 004–004.
    1. Shen G., Deng H., Hu S., Jia Z. Comparison of choline-PET/CT, MRI, SPECT, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis. Skeletal Radiol. 2014;43:1503–1513.
    1. Schwenck J., Rempp H., Reischl G., Kruck S., Stenzl A., Nikolaou K., Pfannenberg C., la Fougère C. Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2017;44:92–101.
    1. Dewulf J., Vangestel C., Verhoeven Y., van Dam P., Elvas F., van den Wyngaert T., Clézardin P. Bone metastases in the era of targeted treatments: insights from molecular biology. Q J Nucl Med Mol Imaging. 2019;63(2):98–111.
    1. Liede A., Wade S., Lethen J., Hernandez R.K., Warner D., Abernethy A.P., Finelli A. An Observational Study of Concomitant Use of Emerging Therapies and Denosumab or Zoledronic Acid in Prostate Cancer. Clin Ther. 2018;40:536–549. e3.
    1. Henry D.H., Costa L., Goldwasser F., Hirsh V., Hungria V., Prausova J., Scagliotti G.V., Sleeboom H., Spencer A., Vadhan-Raj S. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29:1125–1132.
    1. Henry D., Vadhan-Raj S., Hirsh V., von Moos R., Hungria V., Costa L., Woll P.J., Scagliotti G., Smith G., Feng A. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer. 2014;22:679–687.
    1. Fizazi K., Carducci M., Smith M., Damião R., Brown J., Karsh L., Milecki P., Shore N., Rader M., Wang H. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. The Lancet. 2011;377:813–822.
    1. Smith M.R., Coleman R.E., Klotz L., Pittman K., Milecki P., Ng S., Chi K.N., Balakumaran A., Wei R., Wang H. Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events. Ann Oncol. 2015;26:368–374.
    1. Stopeck A.T., Lipton A., Body J.-J., Steger G.G., Tonkin K., de Boer R.H., Lichinitser M., Fujiwara Y., Yardley D.A., Viniegra M. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28:5132–5139.
    1. Coleman R., Gnant M., Morgan G., Clezardin P. Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst. 2012;104:1059–1067.
    1. Scagliotti G.V., Hirsh V., Siena S., Henry D.H., Woll P.J., Manegold C., Solal-Celigny P., Rodriguez G., Krzakowski M., Mehta N.D. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7:1823–1829.
    1. Hernandez R.K., Wade S.W., Reich A., Pirolli M., Liede A., Lyman G.H. Incidence of bone metastases in patients with solid tumors: analysis of oncology electronic medical records in the United States. BMC Cancer. 2018;18:44.
    1. Diessner J., Wischnewsky M., Stüber T., Stein R., Krockenberger M., Häusler S., Janni W., Kreienberg R., Blettner M., Schwentner L. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer. BMC Cancer. 2016;16
    1. Gerratana L., Fanotto V., Bonotto M., Bolzonello S., Minisini A.M., Fasola G., Puglisi F. Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis. 2015;32:125–133.
    1. Maurizi A., Rucci N. The Osteoclast in Bone Metastasis: Player and Target. Cancers (Basel) 2018;10
    1. Chen S.-C., Kuo P.-L. Bone Metastasis from Renal Cell Carcinoma. Int J Mol Sci. 2016;17:987.
    1. Knudsen B.S., Gmyrek G.A., Inra J., Scherr D.S., Vaughan E.D., Nanus D.M., Kattan M.W., Gerald W.L., Vande Woude G.F. High expression of the Met receptor in prostate cancer metastasis to bone. Urology. 2002;60:1113–1117.
    1. Grano M., Galimi F., Zambonin G., Colucci S., Cottone E., Zallone A.Z., Comoglio P.M. Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro. Proc Natl Acad Sci U.S.A. 1996;93:7644–7648.
    1. Hoshino A., Costa-Silva B., Shen T.-L., Rodrigues G., Hashimoto A., Tesic Mark M., Molina H., Kohsaka S., Di Giannatale A., Ceder S. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–335.
    1. Obenauf A.C., Zou Y., Ji A.L., Vanharanta S., Shu W., Shi H., Kong X., Bosenberg M.C., Wiesner T., Rosen N. Therapy-induced tumour secretomes promote resistance and tumour progression. Nature. 2015;520:368–372.
    1. Sun J.-M., Ahn J.S., Lee S., Kim J.A., Lee J., Park Y.H., Park H.C., Ahn M.-J., Ahn Y.C., Park K. Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer. 2011;71:89–93.
    1. Ségaliny A.I., Tellez-Gabriel M., Heymann M.-F., Heymann D. Receptor tyrosine kinases: Characterisation, mechanism of action and therapeutic interests for bone cancers. J Bone Oncol. 2015;4:1–12.
    1. Yamashita Y., Aoki T., Hanagiri T., Yoshii C., Mukae H., Uramoto H., Korogi Y. Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response. Skeletal Radiol. 2012;41:409–414.
    1. Okano Y., Nishio M. [Efficacy of gefitinib in treatment of lung cancer patients with bone metastasis] Clin Calcium. 2008;18:527–533.
    1. Smith D.C., Smith M.R., Sweeney C., Elfiky A.A., Logothetis C., Corn P.G., Vogelzang N.J., Small E.J., Harzstark A.L., Gordon M.S. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2013;31:412–419.
    1. Smith M., De Bono J., Sternberg C., Le Moulec S., Oudard S., De Giorgi U., Krainer M., Bergman A., Hoelzer W., De Wit R. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol. 2016;34:3005–3013.
    1. Di Nunno V., Cimadamore A., Santoni M., Scarpelli M., Fiorentino M., Ciccarese C., Iacovelli R., Cheng L., Lopez-Beltran A., Massari F. Biological issues with cabozantinib in bone metastatic renal cell carcinoma and castration-resistant prostate cancer. Future Oncol. 2018;14:2559–2564.
    1. Lee C., Whang Y.M., Campbell P., Mulcrone P.L., Elefteriou F., Cho S.W., Park S.I. Dual targeting c-met and VEGFR2 in osteoblasts suppresses growth and osteolysis of prostate cancer bone metastasis. Cancer Lett. 2018;414:205–213.
    1. Varkaris A., Corn P.G., Parikh N.U., Efstathiou E., Song J.H., Lee Y.-C., Aparicio A., Hoang A.G., Gaur S., Thorpe L. Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer. Clin Can Res. 2016;22:107–121.
    1. Vandyke K., Fitter S., Dewar A.L., Hughes T.P., Zannettino A.C.W. Dysregulation of bone remodeling by imatinib mesylate. Blood. 2010;115:766–774.
    1. Gobin B., Moriceau G., Ory B., Charrier C., Brion R., Blanchard F., Redini F., Heymann D. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models. PLoS ONE. 2014;9
    1. Sousa S., Clézardin P. Bone-Targeted Therapies in Cancer-Induced Bone Disease. Calcified Tissue Int. 2018;102:227–250.
    1. Browne A.J., Kubasch M.L., Göbel A., Hadji P., Chen D., Rauner M., Stölzel F., Hofbauer L.C., Rachner T.D. Concurrent antitumor and bone-protective effects of everolimus in osteotropic breast cancer. Breast Cancer Res. 2017;19:92.
    1. Xiang L., Gilkes D.M. The Contribution of the Immune System in Bone Metastasis Pathogenesis. Int J Mol Sci. 2019;20
    1. Gilkes D.M. Implications of Hypoxia in Breast Cancer Metastasis to Bone. Int J Mol Sci. 2016;17
    1. Futakuchi M., Fukamachi K., Suzui M. Heterogeneity of tumor cells in the bone microenvironment: Mechanisms and therapeutic targets for bone metastasis of prostate or breast cancer. Adv Drug Del Rev. 2016;99:206–211.
    1. Philippe C., Philippe B., Fouqueray B., Perez J., Lebret M., Baud L. Protection from tumor necrosis factor-mediated cytolysis by platelets. Am J Pathol. 1993;143:1713–1723.
    1. Palumbo J.S., Talmage K.E., Massari J.V., La Jeunesse C.M., Flick M.J., Kombrinck K.W., Jirousková M., Degen J.L. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105:178–185.
    1. Owen K.L., Parker B.S. Beyond the vicious cycle: The role of innate osteoimmunity, automimicry and tumor-inherent changes in dictating bone metastasis. Mol Immunol. 2017;110:57–68.
    1. Zou L., Barnett B., Safah H., Larussa V.F., Evdemon-Hogan M., Mottram P., Wei S., David O., Curiel T.J., Zou W. Bone marrow is a reservoir for CD4+CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res. 2004;64:8451–8455.
    1. Tan W., Zhang W., Strasner A., Grivennikov S., Cheng J.Q., Hoffman R.M., Karin M. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature. 2011;470:548–553.
    1. Nakashima T. [Bone metastasis and RANKL] Clin Calcium. 2014;24:1201–1208.
    1. Ries C.H., Cannarile M.A., Hoves S., Benz J., Wartha K., Runza V., Rey-Giraud F., Pradel L.P., Feuerhake F., Klaman I. Targeting Tumor-Associated Macrophages with Anti-CSF-1R Antibody Reveals a Strategy for Cancer Therapy. Cancer Cell. 2014;25:846–859.
    1. Biswas S.K., Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889–896.
    1. Capietto A.-H., Faccio R. Immune regulation of bone metastasis. Bonekey Rep. 2014;3:600.
    1. Schernberg A., Blanchard P., Chargari C., Deutsch E. Neutrophils, a candidate biomarker and target for radiation therapy? Acta Oncol. 2017;56:1522–1530.
    1. van Dam P.A., Verhoeven Y., Trinh X.B., Wouters A., Lardon F., Prenen H., Smits E., Baldewijns M., Lammens M. RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment. Crit Rev Oncol Hematol. 2019;133:85–91.
    1. Liede A., Hernandez R.K., Wade S.W., Bo R., Nussbaum N.C., Ahern E., Dougall W.C., Smyth M.J. An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer. Oncoimmunology. 2018;7
    1. Angela Y., Haferkamp S., Weishaupt C., Ugurel S., Becker J.C., Oberndörfer F., Alar V., Satzger I., Gutzmer R. Combination of denosumab and immune checkpoint inhibition: experience in 29 patients with metastatic melanoma and bone metastases. Cancer Immunol Immunother. 2019;68(7):1187–1194.
    1. Smidt-Hansen T., Folkmar T.B., Fode K., Agerbaek M., Donskov F. Combination of zoledronic Acid and targeted therapy is active but may induce osteonecrosis of the jaw in patients with metastatic renal cell carcinoma. J Oral Maxillofac Surg. 2013;71:1532–1540.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj