Acquired resistance to anti-EGFR mAb ICR62 in cancer cells is accompanied by an increased EGFR expression, HER-2/HER-3 signalling and sensitivity to pan HER blockers

Our results provide a novel mechanistic insight into the development of acquired resistance to EGFR antibody-based therapy in colorectal cancer cells and justify further investigations on the therapeutic benefits of pan-HER family inhibitors in the treatment of colorectal cancer patients once acquired resistance to EGFR antibody-based therapy is developed

From proteomic analysis to potential therapeutic targets: functional profile of two lung cancer cell lines, A549 and SW900, widely studied in pre-clinical research

Lung cancer is a serious health problem and the leading cause of cancer death worldwide. The standard use of cell lines as in vitro pre-clinical models to study the molecular mechanisms that drive tumorigenesis and access drug sensitivity/effectiveness is of undisputable importance. Label-free mass spectrometry and bioinformatics were employed to study the proteomic profiles of two representative lung cancer cell lines and to unravel the specific biological processes. Adenocarcinoma A549 cells were enriched in proteins related to cellular respiration, ubiquitination, apoptosis and response to drug/hypoxia/oxidative stress. In turn, squamous carcinoma SW900 cells were enriched in proteins related to translation, apoptosis, response to inorganic/organic substances and cytoskeleton organization. Several proteins with differential expression were related to cancer transformation, tumor resistance, proliferation, migration, invasion and metastasis. Combined analysis of proteome and interactome data highlighted key proteins and suggested that adenocarcinoma might be more prone to PI3K/Akt/mTOR and topoisomerase IIα inhibitors, and squamous carcinoma to Ck2 inhibitors. Moreover, ILF3 overexpression in adenocarcinoma, and PCNA and NEDD8 in squamous carcinoma shows them as promising candidates for therapeutic purposes. This study highlights the functional proteomic differences of two main subtypes of lung cancer models and hints several targeted therapies that might assist in this type of cancer.publishe

Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors.

Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab