Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options

Ocaña, Alberto; Pandiella, Atanasio

doi:10.1158/1078-0432.ccr-07-1630

Cited by 43 publications

(32 citation statements)

References 88 publications

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“…Breast cancer remains a leading cause of disease and death among women (1). One type of breast cancer includes tumors that bear high amounts of the transmembrane tyrosine kinase HER2.…”

Section: Introductionmentioning

confidence: 99%

Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer

Hernández-García

González

Sanz

et al. 2015

Nutrition and Cancer

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One of the most aggressive breast cancer subtypes includes tumors with high expression of HER2. Gene expression and functional studies have shown a link between HER2 overexpression and oxidative stress. Because of this, we hypothesized that Oncoxin Oral Solution (OOS), a composite product that contains several antioxidants, could have an antitumoral effect against HER2+ tumors. Dose-response studies, biochemical and cytometric assessment of the effect of OOS on cell cycle and apoptosis, and drug combination analyses were performed on BT474 and SKBR3 cells, 2 HER2-overexpressing breast cancer cell lines. OOS reduced the proliferation of these cells, and augmented the action of lapatinib, a HER2 inhibitor used in the breast cancer clinic. Moreover, OOS decreased growth of HER2+ tumors in mice. Mechanistically, OOS provoked cell cycle blockade through upregulation of p27 expression and downregulation of cyclin D levels. OOS also caused apoptotic cell death in HER2+ breast cancer cells, as indicated by increases in PARP cleavage as well as upregulation of caspase 8 and caspase 3 activities. These results demonstrate an antitumoral action of OOS in preclinical models of HER2+ breast cancer and suggest that it can be used with anti-HER2 therapies currently adopted as standard of care in the oncology clinic.

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“…Breast cancer remains a leading cause of disease and death among women (1). One type of breast cancer includes tumors that bear high amounts of the transmembrane tyrosine kinase HER2.…”

Section: Introductionmentioning

confidence: 99%

Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer

Hernández-García

González

Sanz

et al. 2015

Nutrition and Cancer

Self Cite

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show abstract

“…However, there are at present no realistic options for primary prevention in patients, except hereditary breast cancer related genes, such as BRCA1 and BRCA2 (Marcus et al, 1996), PTEN (Cowden's disease) (Eng et al, 1994), and p53 (Li Fraumeni syndrome) (Magnusson et al, 2012). Recently, multiple molecules have been recognized as pro-oncogenic factors for breast cancers by the universal screen methods basing genomics, transcriptomics, proteotics (Ocana et al, 2008), or other methods. CYP3A4 expression has been recognized as a risk facror of breast cancer in Mexican women (Floriano-Da-Wei Wang 1,2 , Zhao-Hui Wang 3 , Ling-Ling Wang 3 , Yang Song 1 , Gui-Zhen Zhang 1 * Sanchez et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Wang¹,

Wang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The Piwi subfamily comprises two argonaute (Ago) family proteins, which are defined by the presence of PAZ and Piwi domains, with well known roles in RNA silencing. Hiwi, a human Piwi subfamily member, has been shown to play essential roles in stem cell self-renewal and gametogenesis. Recently, accumulating reports have indicated that abnormal hiwi expression is associated with poorer prognosis of multiple types of human cancers, including examples in the breast. However, little is known about details of the oncogenic role of hiwi in breast cancers. In present study, we confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines at both mRNA and protein levels. Thus both RT-qPCR and Western blot data revealed significantly higher hiwi in intratumor than peritumor specimens, overexpression being associated with tumor size, lymph node metastasis and histological grade. Hiwi overexpression was also identified in breast cancer cell lines, MDA-MB-231 and MCF-7, and gain-of-function and loss-of-function strategies were adopted to identify the role of hiwi in the MCF-7 cell growth. Results demonstrated that hiwi expression in MCF-7 cells was significantly up-or down-regulated by the two strategies. We next evaluated the influence of hiwi overexpression or knockdown on the growth of breast cancer cells. Both cell count and colony formation assays confirmed promoting roles of hiwi in MCF-7 cells, which could be inhibited by hiwi specific blockage by siRNAs. In summary, the present study confirmed overexpression of hiwi in breast cancer specimens and breast cancer cell lines, and provided evidence of promotion by hiwi of cell growth. The results imply an oncogenic role of hiwi in breast cancers.

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“…Dozens of anticancer drugs have been developed, with treatment options taking into account tumor grade and histology and whether the desired outcome is curative or palliative. Most regimens combine drugs that act by different mechanisms aimed at improving the odds of suppressing tumor growth (Ocana & Pandiella 2008).…”

Section: Introductionmentioning

confidence: 99%

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

LaPensee

Ben‐Jonathan

2010

Endocrine-Related Cancer

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Resistance to chemotherapy is a major complication in the treatment of advanced breast cancer. Estrogens and prolactin (PRL) are implicated in the pathogenesis of breast cancer but their roles in chemoresistance have been overlooked. A common feature to the two hormones is activation of their receptors by diverse compounds, which mimic or antagonize their actions. The PRL receptor is activated by lactogens (PRL, GH, or placental lactogen) originating from the pituitary, breast, adipose tissue, or the placenta. Estrogen receptors exist in multiple membrane-associated and cytoplasmic forms that can be activated by endogenous estrogens, man-made chemicals, and phytoestrogens. Here, we review evidence that low doses of PRL, estradiol (E 2 ), and bisphenol A (BPA) antagonize multiple anticancer drugs that induce cell death by different mechanisms. Focusing on cisplatin, a DNA-damaging drug which is effective in the treatment of many cancer types but not breast cancer, we compare the abilities of PRL, E 2 , and BPA to antagonize its cytotoxicity. Whereas PRL acts by activating the glutathione-S-transferase detoxification enzyme, E 2 and BPA act by inducing the antiapoptotic protein Bcl-2. The implications of these findings to patients undergoing chemotherapy are discussed.

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Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options

Cited by 43 publications

References 88 publications

Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer

Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

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