Targeted Therapies for the Treatment of Breast Cancer in the Post-trastuzumab Era

Petrelli, Fausto; Cabiddu, Mary; Cazzaniga, M.; Cremonesi, M.; Barni, Sandro

doi:10.1634/theoncologist.2007-0173

Cited by 25 publications

(17 citation statements)

References 35 publications

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“…Overexpression of FAM83A in these cells did not alter tumor growth ( Figure 3C), but rendered cells resistant to lapatinib in vivo ( Figure 3D). Whereas lapatinib can inhibit via both EGFR and HER2 (27), its tumor-inhibitory effect observed here was presumed to have occurred almost exclusively via EGFR. We know from previous work that HER2 is absent or undetectable in T4-2 cells in culture (29)(30)(31), although we did not measure whether the HER2 pathway is reactivated in these cells in vivo.…”

Section: Figurementioning

confidence: 78%

“…To demonstrate the ability of FAM83A to confer resistance to clinical EGFR-TKIs, we first tested effects of lapatinib (27) and gefitinib (28) on control and FAM83A-overexpressing T4-2 cells in 3D cultures. Both drugs reverted wild-type cells to a degree comparable to AG1478-induced reversion, whereas FAM83A-overexpressing cells remained resistant to reversion ( Figure 1E and Supplemental Figure 6A).…”

Section: Figurementioning

confidence: 99%

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FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice

Lee¹,

Meier²,

Furuta³

et al. 2012

J. Clin. Invest.

126

187

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Breast cancers commonly become resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs); however, the mechanisms of this resistance remain largely unknown. We hypothesized that resistance may originate, at least in part, from molecular alterations that activate signaling downstream of EGFR. Using a screen to measure reversion of malignant cells into phenotypically nonmalignant cells in 3D gels, we identified FAM83A as a candidate cancer-associated gene capable of conferring resistance to EGFR-TKIs. FAM83A overexpression in cancer cells increased proliferation and invasion and imparted EGFR-TKI resistance both in cultured cells and in animals. Tumor cells that survived EGFR-TKI treatment in vivo had upregulated FAM83A levels. Additionally, FAM83A overexpression dramatically increased the number and size of transformed foci in cultured cells and anchorage-independent growth in soft agar. Conversely, FAM83A depletion in cancer cells caused reversion of the malignant phenotype, delayed tumor growth in mice, and rendered cells more sensitive to EGFR-TKI. Analyses of published clinical data revealed a correlation between high FAM83A expression and breast cancer patients' poor prognosis. We found that FAM83A interacted with and caused phosphorylation of c-RAF and PI3K p85, upstream of MAPK and downstream of EGFR. These data provide an additional mechanism by which tumor cells can become EGFR-TKI resistant.

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Section: Figurementioning

confidence: 78%

Section: Figurementioning

confidence: 99%

FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice

Lee¹,

Meier²,

Furuta³

et al. 2012

J. Clin. Invest.

126

187

View full text Add to dashboard Cite

show abstract

“…Estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-positive disease with metastatic breast cancer remain incurable (1)(2)(3). For metastatic breast cancer, anthracycline-and/or taxane-based chemotherapy is used as standard treatment (4); however, the outcome remains a common issue.…”

Section: Introductionmentioning

confidence: 99%

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer

Kiba

Morii

Takahashi

et al. 2015

Molecular and Clinical Oncology

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“…Breast cancer, being a heterogeneous disease, does not have one standard treatment; the treatment is customised to each patient and their tumour characteristics (7,8). The patients, therefore, sometimes have to be engaged in considering a range of options.…”

Section: Introductionmentioning

confidence: 99%