Surgical cytoreduction followed by platinum-based chemotherapy has been the standard first-line treatment of patients with high-risk early-stage and advanced epithelial ovarian cancer for nearly two decades. Although the majority of women with advanced disease will respond to combined platinum/taxane therapy, most will ultimately experience recurrence and eventually die as a result of their ova...

The decision of neoadjuvant treatment for high-risk HR+/HER2- EBC remains a challenge. Despite the availability both CHT and ET, risk recurrence persists over time, highlighting need additional therapeutic strategies. In TOT-HER3 trial, we have shown that single dose HER3-DXd, first-in-class HER3 directed antibody drug conjugate, is associated with clinical response, increased immune infiltrati...

PURPOSE ZD1839 is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that has shown clinical activity against EGFR-expressing tumors. Our aim was to explore the effects of ZD1839 in breast cancer cell lines expressing different levels of EGFR and the closely related HER2 receptor. EXPERIMENTAL DESIGN We studied the growth-inhibitory effects of ZD1839 in a series of bre...

Purpose: Formalin-fixed, paraffin-embedded tumor samples from CALGB 80203 were analyzed for expression of EGFR axis– related genes to identify prognostic or predictive biomarkers for cetuximab treatment. Patients and Methods: Patients (238 total) with first-line metastatic colorectal cancer (mCRC) were randomized to FOLFOX or FOLFIRI chemotherapy cetuximab. qRT-PCR analyses were conducted on ti...

The deregulation of the epidermal growth factor receptor (EGFR) pathway plays a major role in the pathogenesis of prostate cancer (PCa). However, therapies targeting EGFR have demonstrated limited effectiveness in PCa. A potential mechanism to overcome EGFR blockade in cancer cells is the autocrine activation of alternative receptors of the human EGFR (HER) family through the overexpression of ...

In breast cancer, neuregulin-1 (NRG1) is known as a ligand for the HER3 receptor, which has no intrinsic tyrosine kinase activity. When activated by NRG1 binding, the HER3 receptor forms a heterodimer with other HER family receptors and mediates downstream signaling pathways, leading to multiple effects including growth, proliferation, decreased apoptosis, cellular migration and angiogenesis. C...

BACKGROUND Inactivation of the NF2 gene predisposes to neurofibromatosis type II and the development of schwannomas. In vitro studies have shown that loss of NF2 leads to the induction of mitogenic signaling mediated by receptor tyrosine kinases (RTKs), MAP kinase, AKT, or Hippo pathways. The goal of our study was to evaluate the expression and activity of these signaling pathways in human schw...

NRG1 (Neuregulin-1) gene fusions are rare oncogenic drivers found in 0.2% of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, and sarcomas. is the predominant ligand HER3 to a lesser extent HER4. fusion proteins retaining an active EGF-like domain drive tumorigenesis proliferation through aberrant activation. Importantly, often mutually exclusi...

Members of the epidermal growth factor receptor, EGFR, family are interesting as targets for radionuclide therapy using targeting agents labeled with α- or β-emitting radionuclides, especially when EGFR-positive colorectal carcinomas, CRC, are resistant to EGFR inhibiting agents like cetuximab and various tyrosine kinase inhibitors. The expression of EGFR, HER2 and HER3 was therefore analyzed i...

Fusion proteins combining hexavalent TRAIL with antibody fragments allow for a targeted delivery and efficient apoptosis induction in tumor cells. Here, we analyzed scFv-Fc-scTRAIL molecules directed against EGFR, HER2, HER3, and EpCAM as well as an untargeted Fc-scTRAIL fusion protein for their potentials to induce cell death both in vitro and in a xenograft tumor model in vivo. The scFv-Fc-sc...