Genomics and Proteomics of Bone Cancer

Marguiles, Aaron G.; Klimberg, V. Suzanne; Bhattacharrya, Sudeepa; Gaddy, Dana; Suva, Larry J.

doi:10.1158/1078-0432.ccr-06-1070

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…At the same time, genomic and proteomic profiling have been shown to correlate with disease progression and tumor aggressiveness. 165 In the future, these technologies may become available in the routine clinical setting, and may be weighed into the risk stratification equation, just like grade, size, nodal status, hormone status, and HER2 status, to determine adjuvant treatment strategies.…”

Section: Identifying High-risk Individualsmentioning

confidence: 99%

Optimal management of bone metastases in breast cancer patients

Wong

Pavlakis

2011

BCTT

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Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.

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Section: Identifying High-risk Individualsmentioning

confidence: 99%

Optimal management of bone metastases in breast cancer patients

Wong

Pavlakis

2011

BCTT

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“…T cells that express RANKL as well as secrete TNF-α are well recognized mediators of bone resorption that can be activated by metastatic tumor cells. Tumor-derived parathyroid hormone related protein (PTHrP) and IL-8 activates transient T cells, thus enhancing bone resorption (Marguiles, et al 2006). …”

Section: The Role Of the Microenvironment In Bone Metastasismentioning

confidence: 99%

Mechanisms of bone metastases of breast cancer

Suva¹,

Griffin²,

Makhoul³

2009

Endocrine-Related Cancer

106

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Cancer development is a multi-step process driven by genetic alterations that elicit the progressive transformation of normal human cells into highly malignant derivatives. The altered cell proliferation phenotype of cancer involves a poorly characterized sequence of molecular events, which often result in the development of distant metastasis. In the case of breast cancer, the skeleton is among the most common of metastatic sites. In spite of its clinical importance, the underlying cellular and molecular mechanisms driving bone metastasis remain elusive. Despite advances in our understanding of the phenotype of cancer cells, the increased focus on the contribution of the tumor microenvironment and the recent revival of interest in the role of tumorpropagating cells (so called cancer stem cells) that may originate or be related to normal stem cells produced in the bone marrow, many important questions remain unanswered. As such, a more complete understanding of the influences of both the microenvironment and the tumor phenotype, which impact the entire multi-step metastatic cascade, is required. In this review, the importance of tumor heterogeneity, tumor-propagating cells, the microenvironment of breast cancer metastasis to bone as well as many current endocrine therapies for the prevention and treatment of metastatic breast cancer is discussed.

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“…The advent of proteomic technologies such as surface enhanced laser desorption ionization (SELDI) time-offlight mass spectrometry (TOF-MS) has provided the means to analyze directly a broad array of proteins of different physical properties in patient samples. (11)(12)(13)(14)(15)(16) This technology has the capability to identify serum biomarker patterns without the need for a priori knowledge of their existence or relevance to a particular disease state. (16)(17)(18)(19) We and others have used SELDI for the discovery of biomarkers important for the diagnosis of a variety of human cancers, including ovarian, (18,19) prostate, (15,20) pancreas, (12,21) breast, (22,23) and colon.…”

Section: Introductionmentioning

confidence: 99%

Serum Biomarker Profile Associated With High Bone Turnover and BMD in Postmenopausal Women

Bhattacharyya

Siegel

Achenbach

et al. 2008

Journal of Bone and Mineral Research

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Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the identification of the individual proteins, this protein fingerprint may provide a novel approach to evaluate high bone turnover states.

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Genomics and Proteomics of Bone Cancer

Cited by 11 publications

References 46 publications

Optimal management of bone metastases in breast cancer patients

Optimal management of bone metastases in breast cancer patients

Mechanisms of bone metastases of breast cancer

Serum Biomarker Profile Associated With High Bone Turnover and BMD in Postmenopausal Women

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