CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC

Abstract Although EGFR mutant–selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK–ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI–resistant persister cells. Many patients with non–small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutatio…

15P A pivotal multicenter translational research project on malignant pleural mesothelioma (MPM): Preliminary results

In the literature: April 2021

Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial

This is a phase II institutional exploratory trial of biweekly irinotecan and cetuximab administration regimen in metastatic colorectal cancer patients progressing to at least one previous chemotherapy line. A total of 40 patients were treated between November 2005 and November 2007 with irinotecan 180 mg m−2 and cetuximab 500 mg m−2 q2w (every 2 weeks), in every 21-day cycles, until unacceptable toxicity or progressive disease. An overall response rate of 22.5% was obtained (two complete and seven partial responses). The disease control rate was 60%. The time to progression was 3.4 months and the overall survival was 8 months. The toxicity compared very favourably to weekly cetuximab combi…

In the literature: August 2018.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by a very poor prognosis. Despite some minor therapeutic advances, median overall survival of patients with metastatic disease ranges from 6 to 11 months. Even for those who undergo potential curative surgery, expected median survival is below 27 months. Current treatment for both localised and metastatic disease is often based on unspecific characteristics, such as performance status and comorbidities. As many patients with PDAC are chemorefractory, there is an unmet clinical need to define responsiveness. Moreover, precision medicine approaches for pancreatic cancer are challenging. In an article recently published in Cancer Discove…

Treatment of HER2 positive advanced breast cancer with T-DM1: A review of the literature

Abstract Background Trastuzumab emtansine (T-DM1), a new agent developed for the treatment of HER2-positive breast cancer, is an antibody-drug conjugate with a complex compound obtained by the conjugation of trastuzumab, a stable thioether linker, and the potent cytotoxic drug maytansine-derivate(DM1), which inhibits cell division and induces cell death. Field of study PubMed database, ESMO, ASCO, San Antonio Breast Cancer Symposium Meeting abstracts and clinicaltrials.gov were searched using the terms “Anti-HER2 treatment breast cancer and trastuzumab emtansine (T-DM1) “; papers considered relevant for the aim of this review were selected. Findings/results The phase I trials have determine…