Altogether, our in vitro and in vivo data indicate that the ERBB2 gene is a novel MBP-1 target, and immunohistochemistry analysis of primary tumors suggests that the concomitant high expression of MBP-1 and HDAC1 may be considered a diagnostic marker of cancer progression for breast IDC.
As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain.
Since relevant differences between primary tumors and metastases could arise during tumor progression as evidenced by phenotypic discordances reported for hormonal receptors or HER-2 expression, in this analysis we studied changes that occurred in our TNBC model IIB-BR-G throughout the development of IIB-BR-G-MTS6 metastasis to the lymph nodes (LN) in nude mice, using an antibody-based protein array to characterize their expression profile.
We reviewed 91 patients with HER2-positive MBC treated with trastuzumab and investigated correlations between survival and clinical response to first trastuzumab-based therapy and biological markers, time to first tumor progression (1st TTP), response rate (RR), estrogen receptor (ER), Ki-67, and p53 overexpression.
These findings suggest that in ileal NEN, HER-2/neu overexpression plays a role in the carcinogenetic process and by triggering the altered expression of c-Met and MTA-1, may activate the molecular pathway(s) promoting tumor progression and metastasis development.
This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy.
In recent studies reviewed here, the synergistic effect of TGFβ and HER2 on tumor progression has been shown to likely be a combined result of two distinct features: (1) loss of TGFβ's tumor suppressive effect through functional alterations in the anti-mitogenic effect of Smad-mediated transcription, and (2) gain of pro-survival and pro-migratory function through HER2-dependent mechanisms.
The Kaplan-Meier and log-rank tests further revealed that positivity of AR (P=0.0005), EGFR (P=0.2425), pEGFR (P=0.1579), ERBB2 (P=0.2997), or pERK (P=0.1270) and negativity of pAKT (P=0.0483) were associated with tumor progression.
However, most patients with advanced ERBB2 amplified breast cancers whose tumors initially respond to trastuzumab develop resistance to the drug, leading to tumor progression.
The aim of this prospective study, in which fluorescence in situ hybridization was used to determine human epidermal growth factor receptor 2 status in primary breast cancers and in the lymph node metastases, was to verify the stability of human epidermal growth factor receptor 2 status in the following steps of neoplastic progression of breast cancer, which is fundamental for an appropriate therapeutic approach.
The Erbb-2 (neu in rat and Her-2 in humans) tyrosine kinase receptor is an oncoantigen (i.e., a tumor-associated molecule directly involved in cancer progression).
Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression.
To elucidate the involvement of shed HER2/ECD in HER2-driven tumor progression and in guiding therapy of individual patients, we examined biological effects exerted by elevated HER2/ECD in cancer growth and in response to Trastuzumab.
We show here that overexpression of beta(1)-integrin is an independent negative prognostic factor for tumor progression of HER-2-positive MBC patients treated with trastuzumab-based chemotherapy.
Epidermal growth factor receptor (EGFR), HER2/neu, c-Met, and vascular endothelial growth factor receptor-1 (VEGFR1) (tyrosine kinase growth factor receptors) are implicated in tumor progression, but little is known about their role in anal lesions.
These data suggest that EphA2 cooperates with ErbB2 to promote tumor progression in mice and may provide a novel therapeutic target for ErbB2-dependent tumors in humans.
These results suggest that by acting on ErbB ligand shedding, an excess of TGF-beta may result in (i) conditioning of the tumor microenvironment with growth factors that can engage adjacent stromal and endothelial cells; (ii) potentiation of signaling downstream ErbB receptors, thus contributing to tumor progression and resistance to anti-HER2 therapies; and (iii) poor clinical outcomes in women with breast cancer.