We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell death, however, the underlying mechanisms remain unclear.
Overexpressed epidermal growth factor receptor (EGFR) and overactivated epithelial-mesenchymal transition (EMT) in triple-negative breast cancer (TNBC) can enhance tumorigenesis and tumor recurrence and metastasis.
Triple-negative breast cancer (TNBC), which lacks expression of estrogen receptor (ER), progesterone receptor (PgR), and epidermal growth factor receptor 2 (HER2), currently has no effective hormonal or molecular target therapy.
We demonstrate that a dual cdc7/CDK9 inhibitor, PHA-767491, synergises with multiple EGFR-TKIs (lapatinib, erlotinib and gefitinib) to overcome resistance to EGFR-targeted therapy in various TNBC cell lines.
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and absence of amplification of human epidermal growth factor receptor (HER2).
Thus, peptide 22 is a promising EGFR specific TNBC cell binding peptide that can be conjugated directly to a chemotherapeutic drug or to nanoparticles for targeted drug delivery to enhance the efficacy of chemotherapy for TNBC treatment.
Triple negative breast cancer (TNBC) is the most notorious form of breast cancer which involves absence of the estrogen, progesterone and human epidermal growth factor receptor (EGFR) on breast cancer cells.
The aim of the present study was to examine the partial agonistic properties of cetuximab, which not only blocks ligand binding, but also partially triggers EGFR activation, which may lead to cetuximab resistance in TNBC.
However, epidermal growth factor receptor (EGFR) is highly expressed in most of the TNBCs, which may provide a potential target for EGFR targeting therapy.
EGFR overexpression is in 50-75% TNBC and EGFR-mediated signaling has potential as an attractive therapeutic target in some specific subtypes of breast cancer due to its significant association with tumor metastasis and poor prognosis.
We previously showed that reduced expression of annexin A6 (AnxA6), a calcium-dependent membrane-binding tumor suppressor, not only promoted the internalization and degradation of activated EGFR but also sensitized TNBC cells to EGFR-TKIs.
Together, our results identify NSD2 as a major epigenetic regulator in TNBC and provide a rationale for targeting NSD2 alone or in combination with EGFR inhibitors as a targeted therapy for TNBC.
The mutational profile of TNBC during treatment as inferred from patterns of mutant allele frequencies in matched pre-and post-NAC samples showed that RD harbored alterations of cell cycle progression, PI3K/Akt/mTOR, and EGFR tyrosine kinase inhibitor-resistance pathways.
On the one hand, HTO might stimulate ERK signaling and induce TNBC cell autophagy, while on the other, it could increase dihydroceramide and ceramide production, which would inhibit Akt independently of EGFR activation and provoke cell death.
<b>Purpose:</b> The EGFR is frequently overexpressed in TNBC, and the EGFR-overexpressing TNBC presumably escapes EGFR inhibitor therapy by upregulating autophagy and inhibiting apoptosis.
Surprisingly, pterostilbene alone did not inhibit, nor downregulate Src phosphorylation in the EGFR-mutation positive NSCLC cell lines or the TNBC cell line, MDA-MB-231.
In the present study, we investigated whether miR-361-5p can act as a tumor suppressor by targeting required for cell differentiation 1 homolog (RQCD1) and inhibiting epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway in TNBC.
These data not only suggest that AnxA6 modulated Ca<sup>2+</sup> influx and effector functions of RasGRF2 underlie at least in part, the AnxA6 mediated TNBC cell growth and/or motility, but also provide a rationale to target Ras-driven TNBC with EGFR targeted therapies in combination with inhibition of RasGRF2.