Afatinib and its encapsulated polymeric micelles inhibits HER2-overexpressed colorectal tumor cell growthin vitroandin vivo

Abstract

Colorectal cancer (CRC) is known as a common malignant neoplasm worldwide. The role of EGFR/HER2 in CRC is unclear. Afatinib is an irreversible EGFR/HER2 inhibitor. There were few studies of afatinib on CRC. Here, we investigated the protein levels/expressions of HER2 in sera and tumors from CRC patients and the therapeutic effect of afatinib on HER2-overexpressed CRC in vitro and in vivo. The increased HER2 levels were detected in the collected sera and tumors of patients with CRC. The serological HER2 levels were correlated with the tumor HER2 expressions in patients. Afatinib also inhibited the HER2-positive tumor cell growth and caused apoptosis in HER2-overexpressed human colorectal cancer HCT-15 cells but not in low HER2 expressed human gastric cancer MKN45 cells. In vivo study showed that afatinib reduced tumor growth in HER2-overexpressed xenografts. Moreover, afatinib-encapsulated micelles displayed higher cytotoxic activity in HCT-15 cells and were more effective for tumor growth suppression in HCT-15-induced tumor xenografts than afatinib performance alone. Taken together, these findings suggest that higher serum HER2 levels reflect the higher HER2 contents in tumors of CRC patients, and the improved afatinib-encapsulated micelles possess high therapeutic efficacy in HER2-overexpressed CRC in vitro and in vivo.

Patterns of Chromosomal Aberrations in Solid Tumors

“…This led to the initiation of various clinical trials aimed at testing combinations of trastuzumab or other HER2-targeting agents with platinum/ fluoropyrimidine-based chemotherapy for patients with HER2-positive cancers (Kasper and Schuler 2014; Okines et al 2011). Very recent data indicate that targeting HER2 may represent a therapeutic strategy in patients with CRC as well (Conradi et al 2013; Guan et al 2014; Seo et al 2014). …”

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

“…Some reports also suggest that afatinib can be a promising inhibitor against human pancreatic tumour cells [24,30,31]. Positive results have also been reported in the therapy of other advanced solid tumours, when afatinib is given in combination with conventional chemotherapeutic agents [26,32]. In this study, we assessed in vitro the effect of afatinib conjugated with PEGAuNPs in pancreatic cancer cells (cell line S2-013), and NSCLC cells (cell line A549).…”

Stimulation of Eryptosis by Afatinib

“…Side effects of afatinib include skin rash [6], xerosis [6], paronchia [6], stomatitis [6,41], diarrhea [6,41], heart failure [42], neutropenia [41], leukopenia [41], and anemia [41,43]. Afatinib is in part effective by inducing apoptosis [44][45][46][47][48][49][50][51][52][53][54][55][56][57], an effect involving oxidative stress [46].…”