Mechanisms of osteolytic and osteoblastic skeletal lesions

Roodman, G. David; Silbermann, Rebecca

doi:10.1038/bonekey.2015.122

Cited by 53 publications

(46 citation statements)

References 54 publications

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“…Breast cancer, for example, most commonly forms osteolytic lesions, while prostate cancer commonly induces the formation of osteoblastic lesions. 23 It has been proposed that the formation of osteoblastic lesions in prostate cancer is preceded by a resorptive phase, given the success of anti-resorptive therapies (e.g. bisphosphonates) in reducing bone pain in prostate cancer patients.…”

Section: Clinical Implications Of Bone Metastasismentioning

confidence: 99%

Tumor dormancy in bone

Mayhew¹,

Omokehinde²,

Johnson

2019

Cancer Reports

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Background Bone marrow is a common site of metastasis for a number of tumor types, including breast, prostate, and lung cancer, but the mechanisms controlling tumor dormancy in bone are poorly understood. In breast cancer, while advances in drug development, screening practices, and surgical techniques have dramatically improved survival rates in recent decades, metastatic recurrence in the bone remains common and can develop years or decades after elimination of the primary tumor. Recent Findings It is now understood that tumor cells disseminate to distant metastatic sites at early stages of tumor progression, leaving cancer survivors at a high risk of recurrence. This review will discuss mechanisms of bone lesion development and current theories of how dormant cancer cells behave in bone, as well as a number of processes suspected to be involved in the maintenance of and exit from dormancy in the bone microenvironment. Conclusions The bone is a complex microenvironment with a multitude of cell types and processes. Many of these factors, including angiogenesis, immune surveillance, and hypoxia, are thought to regulate tumor cell entry and exit from dormancy in different bone marrow niches.

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Section: Clinical Implications Of Bone Metastasismentioning

confidence: 99%

Tumor dormancy in bone

Mayhew¹,

Omokehinde²,

Johnson

2019

Cancer Reports

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“…In prostate cancer, Prostate Specific Antigen (PSA) activates TGF- β, an osteoblast growth factor. Also, there is an increased production of local PTHrP that is thought to increase osteoblast progenitor cell proliferation and early osteoblast differentiation (9). These osteoblastic lesions are also associated with significant bone pain and increased fracture risk.…”

Section: 0 Pathophysiology Of Bone Disease In Cancer Patientsmentioning

confidence: 99%

Evaluation and management of skeletal disease in cancer care

Kommalapati

Tella

Esquivel

et al. 2017

Critical Reviews in Oncology/Hematology

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Recently, there have been considerable advancements in cancer therapies thereby prolonging the life of cancer survivors. However, these recent advancements present new challenges in the management of bone disease in cancer survivors. Bone acts as a fertile soil for cancer seeding and bone health is often compromised because of increased inflammatory cytokines in cancer, direct cancer metastasis and toxic effects of anti-cancer therapies. This effect is more pronounced in elderly population who already have compromised bone mineral density leading to increased skeletal related events and bone pain. Timely diagnosis and effective interventions are essential for reducing bone-related morbidity in cancer survivors. Also, a complex interdependence exists between cancer related bone disease and tumor growth, creating a vicious circle of extensive bone destruction and cancer progression. Hence, maintenance of bone health and integrity plays a pivotal role in comprehensive cancer care. The bone-targeted treatments have been shown to preserve bone health, and modify the course of the underlying cancer. Management of long-term bone health requires a broad knowledge base that both endocrinologists, oncologists and other care team members should be aware of. The manuscript highlights the skeletal effects of cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy induced bone loss and steps for accurate diagnosis and management of bone disease in cancer survivors by bridging the gaps in the comprehensive cancer care.

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“…The process of cancer metastases, following tumor growth at the primary site of origin, involves intravasation and survival in the bloodstream, arrest, extravasation and finally establishment, by invasion and angiogenesis, at a distant site [17–18]. Tumor cells that metastasize in bone induce destructive osteolytic and/or bone forming osteoblastic lesions [12, 19] and ‘teach’ this affected bone microenvironment to produce factors that stimulate tumor cell growth [20–21]. In general, once bone metastases are present, patient survival is dramatically reduced.…”

Section: Introductionmentioning

confidence: 99%

A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

et al. 2016

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While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.

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Mechanisms of osteolytic and osteoblastic skeletal lesions

Cited by 53 publications

References 54 publications

Tumor dormancy in bone

Tumor dormancy in bone

Evaluation and management of skeletal disease in cancer care

A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

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