Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer‐induced bone loss

Dionísio, Maria Rita; Mansinho, André; Abreu, Catarina; Cavaco-Silva, Joana; Casimiro, Sandra; Costa, Luís

doi:10.1111/bcp.13852

Cited by 23 publications

(14 citation statements)

References 73 publications

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“…However, some BPs also seem to have direct anti‐tumour activity. In preclinical models zoledronate was shown to inhibit cell migration, invasion and metastasis and several clinical studies have shown a beneficial effect for adjuvant use of the drug in elderly postmenopausal women in addition to a role in preventing bone metastases (see also papers in this Themed Issue by Dionisio et al and Chukir et al). Zoledronate might exert its anti‐tumour effects through the miR‐21/PTEN/Akt signalling and Activin signalling pathways …”

Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacology of bisphosphonates

Cremers

Drake

Ebetino

et al. 2019

Brit J Clinical Pharma

173

107

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The biological effects of the bisphosphonates (BPs) as inhibitors of calcification and bone resorption were first described in the late 1960s. In the 50 years that have elapsed since then, the BPs have become the leading drugs for the treatment of skeletal disorders characterized by increased bone resorption, including Paget's disease of bone, bone metastases, multiple myeloma, osteoporosis and several childhood inherited disorders. The discovery and development of the BPs as a major class of drugs for the treatment of bone diseases is a paradigm for the successful journey from "bench to bedside and back again". Several of the leading BPs achieved "blockbuster" status as branded drugs. However, these BPs have now come to the end of their patent life, making them highly affordable. The opportunity for new clinical applications for BPs also exists in other areas of medicine such as ageing, cardiovascular disease and radiation protection. Their use as inexpensive generic medicines is therefore likely to continue for many years to come. Fifty years of research into the pharmacology of bisphosphonates have led to a fairly good understanding about how these drugs work and how they can be used safely in patients with metabolic bone diseases. However, while we seemingly know much about these drugs, a number of key aspects related to BP distribution and action remain incompletely understood. This review summarizes the existing knowledge of the (pre)clinical and translational pharmacology of BPs, and highlights areas in which understanding is lacking.

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Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacology of bisphosphonates

Cremers

Drake

Ebetino

et al. 2019

Brit J Clinical Pharma

173

107

View full text Add to dashboard Cite

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“…These GTP binding proteins are critical for osteoclast resorption of bone [ 75 ]. N-amino bisphosphonates ultimately cause osteoclast apoptosis [ 76 ] and inhibit osteoclasts by multiple mechanisms, including interfering in the differentiation of hematopoietic precursors into multinucleated giant cells ( Figure 1 ), ruffling of osteoclast surface, binding of the osteoclast to the bone surface, and secretion of hydrochloric acid, one of the main mechanisms of bone resorption [ 77 ].…”

Section: Oral and Intravenous Bisphosphonates And Rank Ligand Inhimentioning

confidence: 99%

Osteoporosis: A Long-Term and Late-Effect of Breast Cancer Treatments

Shapiro

2020

Cancers

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Osteoporosis is both a long-term effect (occurs during treatment and extends after treatment) and a late-effect (occurs after treatment ends) of breast cancer treatments. The worldwide prevalence of osteoporosis is estimated to be some 200 million patients. About one in three postmenopausal women will experience an osteoporotic (or fragility) fracture of the hip, spine, or wrist. breast cancer treatments, including gonadotropin-releasing hormone (GnRH) agonists, chemotherapy-induced ovarian failure (CIOF), and aromatase inhibitors (AIs), cause bone loss and increase the risks of osteoporosis. Also, breast cancer is a disease of aging, and most of the “one in eight” lifetime risks of breast cancer are in women in their sixth, seventh, and eighth decades. The majority of women diagnosed with breast cancers today will be long-term survivors and experience personal cures. It is the coalescence of osteoporosis with breast cancer, two common and age-related conditions that make osteoporosis relevant in women with breast cancer throughout the continuum from diagnosis, treatment, and survivorship. It is critical to remember that women (and men) will lose bone after age thirty years. However, only certain women will lose bone of sufficient magnitude to merit treatment with anti-osteoporosis drugs. The narrative review is intended for medical, surgical, radiation oncologists, and other mid-level providers, and provides an overview of bone loss and the prevention and treatment of osteoporosis.

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“…Initial preclinical data evidenced a possible role in systemic tumor control with better progression and overall survival, but strongly results are warranted. In addition, in this case the systemic anti-cancer effect seems due to a better immune system regulation, T-cell activation and immunogenic chemokine's increase [61]. Current clinical studies are evaluating to a greater extent the effect of denosumab on survival and other biomarkers.…”

Section: Bone Targeted Drugs Have a Role In Anticancer Systemic Theramentioning

confidence: 99%

Immune system and bone microenvironment: rationale for targeted cancer therapies

et al. 2020

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Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

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Clinical and translational pharmacology of drugs for the prevention and treatment of bone metastases and cancer‐induced bone loss

Cited by 23 publications

References 73 publications

Pharmacology of bisphosphonates

Pharmacology of bisphosphonates

Osteoporosis: A Long-Term and Late-Effect of Breast Cancer Treatments

Immune system and bone microenvironment: rationale for targeted cancer therapies

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