<i>De Novo</i>
            Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

Madrid-Paredes, Adela; Cañadas-Garre, Marisa; Sánchez–Pozo, Antonio; Calleja‐Hernández, Miguel Ángel

doi:10.2217/pgs.15.88

Cited by 7 publications

(2 citation statements)

References 94 publications

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“…Trastuzumab is a humanized anti-HER2 monoclonal antibody, which was approved for the treatment of HER2-positive cancers. Although trastuzumab is effective in various clinical cases, it eventually fails as primary and/or acquired resistance occurs in up to 62% of patients during the first year of treatment ( 1 – 3 ). For instance, many HER2/ neu -positive cancers do not respond to trastuzumab treatment ( de novo resistance), while many trastuzumab-responsive patients develop resistance after continuous trastuzumab infusion within 1 year (acquired resistance) ( 4 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

Geng

et al. 2017

Oncology Reports

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Ovarian cancer is one of the most common gynecologic cancers and the leading cause of mortality in women worldwide. HER2/neu is overexpressed in various types of cancers and is most commonly associated with decreased survival. Trastuzumab is a humanized anti-HER2 monoclonal antibody for the treatment of HER2-positive breast cancers. However, primary and/or acquired resistance occurs in up to 62% patients during the first year of treatment. Vascular endothelial growth factor (VEGF) is a well-known angiogenesis factor involved in many physiological and pathological processes. Its significance has been implicated in promoting tumor growth and metastasis via angiogenesis. In the present study, we demonstrated that the upregulation of SP1 enhanced expression of VEGF promoting the angiogenesis and migration of trastuzumab-resistant ovarian cancer cell line SKOV3-T. Our in vitro and in vivo results both gave evidence that the SP1-VEGF axis was responsible for the enhanced malignancy, angiogenesis and migration in the acquired trastuzumab-resistant ovarian cancer cell model.

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Section: Introductionmentioning

confidence: 99%

SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

Geng

et al. 2017

Oncology Reports

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“…In this study, we aimed to identify GPCR-targeting drugs for repurposing in triple-negative BC (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) BC due to the unmet clinical need to discover novel targets and drugs ( Kolbasnikov, 1987 ; Dai et al, 2015 ; Madrid-Paredes et al, 2015 ; de Melo Gagliato et al, 2016 ; Goutsouliak et al, 2020 ). We performed a high throughput screening (HTS) aimed at assessing the efficacy and potency of a large panel of drugs/compounds targeting various GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of anti-HER2 therapies.…”

Section: Introductionmentioning

confidence: 99%

Screening of GPCR drugs for repurposing in breast cancer

et al. 2022

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Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on β-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of β3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.

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Neoplasms of the Breast

Rugo

Majure

Dragun

et al. 2017

Holland‐Frei Cancer Medicine

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Overview Breast cancer in women remains a major medical problem with significant public health and societal ramifications, including issues related to screening, risk factors, prevention, diagnosis, treatment, and survival following diagnosis. Major advances have markedly improved the understanding of clinical phenotypes, as well as the biologic pathways that drive tumor growth and resistance. This research has led to dramatic changes in treatment that have contributed to a significant reduction in breast cancer mortality over the last two decades, and is the basis of ongoing clinical research. Molecular profiling has provided insights into the heterogeneity of breast cancer subtypes; combining biology and tumor burden has allowed stratification of both risk and treatment to begin the process of individualizing screening, prevention, and treatment. As new information accumulates, new paradigms of management become the standard of care reflected in international guidelines. Our challenge is to apply new formation and treatment appropriately and effectively, and to understand both response and resistance. Information obtained from molecular, biologic, and pathologic investigations and clinical trials provides the major focus of this chapter.

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De Novo Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

Cited by 7 publications

References 94 publications

SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an acquired trastuzumab-resistant ovarian cancer model

Screening of GPCR drugs for repurposing in breast cancer

Neoplasms of the Breast

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