Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases

Oyewumi, Moses O.; Alazizi, Adnan; Wehrung, Daniel; Manochakian, Rami; Safadi, Fayez F.

doi:10.1155/2014/236246

Cited by 13 publications

(12 citation statements)

References 64 publications

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“…About 30 to 40 percent of people with advanced lung cancer have bone metastasis. In fact, as survival rates for lung cancer are increasing, the number of people living with bone metastases is also increasing [ 2 , 3 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Hammamy

Farooqui

Ghadban

2018

Case Reports in Medicine

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Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is very common and it accounts approximately to one-third of all primary pulmonary cancers. Although a minority of patients with lung cancer are asymptomatic, which gets usually detected in routine chest radiography, most of the patients present with some symptoms. Lung cancer metastasis may occur virtually in every organ system. Patients with non-small-cell lung cancer commonly have extrathoracic metastases to the adrenal glands, liver, brain, bones, and lymph nodes at presentation. Approximately one-third of patients with lung cancer will present with symptoms related to extrathoracic spread. Metastasis to the bone is not uncommon in lung cancer; however, osteoblastic bone metastasis is very rare. Here we present a 30-year-old female diagnosed to have pulmonary adenocarcinoma with multiple sclerotic bony lesions in the vertebra.

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Section: Discussionmentioning

confidence: 99%

Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Hammamy

Farooqui

Ghadban

2018

Case Reports in Medicine

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“…Considering the prognosis of bone metastases, the main goal of therapy is to retard the metastatic progression by impeding the ability of tumor cell invasion and proliferation in the bone microenvironment [45,46]. Understanding the key pathways regulating homing, colonization and proliferation of MTC in the bone is relevant for the recently development of targeted therapies targeted mainly against OPG/RANK/RANKL pathway, PTHrP, chemokines, and chemokines receptors.…”

Section: Metastasis To Bonementioning

confidence: 99%

Metastatic Tumors to the Jaws and Mouth

Hirshberg

Berger

Allon

et al. 2014

Head and Neck Pathol

160

171

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Metastatic dissemination to the oral cavity is rare and is usually the evidence of a wide spread disease with an average survival rate of 7 months. In almost a quarter of the cases, oral metastasis was found to be the first indication of an occult malignancy at a distant site. Metastatic lesions can be found anywhere in the oral cavity, however, the jawbones with the molar area is the most frequently involved site. In the oral soft tissues, the gingiva is the most common site, suggesting the possible role of inflammation in the attraction of metastatic deposits. The most common primary malignancies presenting oral metastases were the lung, kidney, liver, and prostate for men, and breast, female genital organs, kidney, and colorectum for women. Most patients with jawbone metastasis complain of swelling, pain, and paresthesia. An exophytic lesion is the most common clinical presentation of metastatic lesions in the oral soft tissues. Early lesions, mainly those located in the gingiva, may resemble a hyperplastic or reactive lesion. Once a lesion is recognized as metastasis, the primary tumor site should be identified following clinical, radiological and histopathological investigations. If standardized diagnostic workup fails to detect the site of origin, then the term carcinoma of unknown primary is applied. Personalized medicine tools such as tissue-oforigin assays should be applied, either by immunohistochemical testing or by molecular-profiling methods as these may lead to a more favorable outcome.

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“…Lung cancer is the most common cause of cancer death worldwide [ 1 , 2 ]. In 2016, new cases in the United States could reach 230,000 with more than 150,000 deaths ( cancer.org ).…”

Section: Introductionmentioning

confidence: 99%

Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells

et al. 2016

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The potential application of GPNMB/OA as a therapeutic target for lung cancer will require a greater understanding of the impact of GPNMB/OA ectodomain (ECD) protein shedding into tumor tissues. Thus, in this work we characterized GPNMB/OA expression and extent of shedding of its ECD protein while evaluating the impact on lung cancer progression using three non-small cell lung cancer (NSCLC) cell lines: A549, SK-MES-1 and calu-6. We observed a direct correlation (R2 = 0.89) between GPNMB/OA expression on NSCLC cells and the extent of GPNMB/OA ECD protein shedding. Meanwhile, siRNA-mediated knockdown of GPNMB/OA in cancer cells significantly reduced GPNMB/OA ECD protein shedding, migration, invasion and adhesion to extracellular matrix materials. Also, exogenous treatment of cancer cells (expressing low GPNMB/OA) with recombinant GPNMB/OA protein (rOA) significantly facilitated cell invasion and migration, but the effects of rOA was negated by inclusion of a selective RGD peptide. Further studies in athymic (nu/nu) mice-bearing calu-6 showed that intratumoral supplementation with rOA effectively facilitated in vivo tumor growth as characterized by a high number of proliferating cells (Ki67 staining) coupled with a low number of apoptotic cells. Taken together, our results accentuate the relevance of GPNMB/OA ECD protein shedding to progression of lung cancer. Thus, strategies that suppress GPNMB/OA expression on lung cancer cells as well as negate shedding of GPNMB/OA ECD protein are worthy of consideration in lung cancer therapeutics.

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Emerging Lung Cancer Therapeutic Targets Based on the Pathogenesis of Bone Metastases

Cited by 13 publications

References 64 publications

Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma

Metastatic Tumors to the Jaws and Mouth

Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells

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