Survival Benefit With Radium-223 Dichloride in a Mouse Model of Breast Cancer Bone Metastasis

Suominen, Mari I.; Rissanen, Jukka P.; Käkönen, Rami S.; Fagerlund, Katja M.; Alhoniemi, Esa; Mumberg, Dominik; Ziegelbauer, Karl; Halleen, Jussi M.; Käkönen, Sanna Maria; Scholz, Arne

doi:10.1093/jnci/djt116

Cited by 86 publications

(84 citation statements)

References 15 publications

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“…The in vitro action of 223 Ra was investigated by Suominen and co-workers, who showed an inhibitory effect on proliferation of breast cancer cells and differentiation of osteoblasts and osteoclasts (28).…”

Section: Experimental Datamentioning

confidence: 99%

“…A very interesting finding was that more pronounced effects were observable if 223 Ra was administered in a preventative or micrometastatic setting (28).…”

Section: Experimental Datamentioning

confidence: 99%

“…Animal studies have demonstrated that 223 Ra administration in a preventative or micrometastatic setting increased the time to death in both settings (28). To translate these results to humans is not a simple matter as far as administration time and selection of patients at high risk of developing bone metastases are concerned.…”

Section: Administration Timingmentioning

confidence: 99%

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Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Buroni

Persico

Pasi

et al. 2016

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Abstract. 223 Prostate cancer (PCa) is the most common malignancy in men (1). In patients affected by advanced PCa, defined as hormonesensitive disease since the tumor still requires androgen for growth, androgen deprivation therapy (ADT), including luteinizing hormone-releasing hormone (LHRH) agonists, antagonists and anti-androgens, represents the first-line treatment. Unfortunately some cancer cells develop resistance to ADT, indicating the progression of the disease to metastatic castration-resistant prostate cancer (mCRPCa). Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4, 5).Bones are the preferred site of metastasis. Almost 90% of men who die from PCa have bone-metastatic disease (6), with a 5-year OS rate of 20%. Due to the fragility of bone with metastases, with the related risk of pain, fractures, spinal cord compression and hematological consequences, several drugs have been developed to treat the osseous involvement of this disease. In previous years, the optimal treatment aimed to relieve pain and reduce skeletal morbidity.Besides systemic therapies, bone-targeted agents that focus their activity on bone, such as bisphosphonates, monoclonal antibody and radiopharmaceuticals, have become available. The bisphosphonate zoledronic acid, the antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) denosumab and radiopharmaceuticals [such as 89 Sr and 153 Sm-ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP)], were approved for delaying skeletal-related events (SREs) and for the palliation of bone pain from mCRPCa. Radionuclide TherapyRadionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cancer cells (7). Bone-targeted radiopharmaceuticals localize their radiation to sites of high bone remodeling. 5719

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Section: Experimental Datamentioning

confidence: 99%

“…A very interesting finding was that more pronounced effects were observable if 223 Ra was administered in a preventative or micrometastatic setting (28).…”

Section: Experimental Datamentioning

confidence: 99%

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Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Buroni

Persico

Pasi

et al. 2016

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“…In a mouse model of established bone metastases, treatment with radium-233 significantly decreased osteolysis, tumor burden and tumor cachexia, as well as increasing the survival of treated mice. 48 Data from clinical trials in breast cancer patients are limited, but a case report described clinical benefit to young women suffering from hormone refractory and chemotherapy refractory metastatic breast cancer. 49 In a phase 2 trial in 23 advanced breast cancer patients with progressive bone-dominant disease, radium-223 led to a significant reduction in uNTX-1 and bone-alkaline phosphatase.…”

Section: Mtor Inhibitionmentioning

confidence: 99%

Cancer-targeted therapies and radiopharmaceuticals

Rachner¹,

Jakob

Hofbauer

2015

BoneKEy Reports

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The treatment of bone metastases remains a clinical challenge. Although a number of well-established agents, namely bisphosphonates and denosumab, are available to reduce the occurrence of skeletal-related events, additional cancer-targeted therapies are required to improve patients' prognosis and quality of life. This review focuses on novel targets and agents that are under clinical evaluation for the treatment of malignant bone diseases such as activin A, src and endothelin-1 inhibition or agents that are clinically approved and may positively influence bone, such as the mTOR inhibitor everolimus. In addition, the potential of alpharadin, a novel radiopharmaceutical approved for the treatment of prostatic bone disease, is discussed.

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“…Ra-223 treatment delays time to first symptomatic SRE, prolongs overall survival and also a safe treatment modality in castration resistant prostate carcinoma patients with only bone metastasis (Parker et al, 2013). Efficacy of Ra-223 in breast cancer bone metastasis has been shown in vivo and in a mouse model (Suominen et al, 2013).…”

Section: Radionuclide Therapy For Breast Cancer Bone Metastasismentioning

confidence: 99%

Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs

Erdoğan

Çiçin²

2014

Asian Pacific Journal of Cancer Prevention

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Breast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor kB ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.

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Survival Benefit With Radium-223 Dichloride in a Mouse Model of Breast Cancer Bone Metastasis

Abstract: Our findings strongly support the development of radium-223 dichloride for the treatment of breast cancer patients with or at high risk of developing bone metastases.

Cited by 86 publications

References 15 publications

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

Cancer-targeted therapies and radiopharmaceuticals

Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs

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