Moreover, by targeting uPAR and EGFR interaction with an integrin antagonist peptide we restored vemurafenib responsiveness in melanoma resistant cells.
The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non-small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFRT790M in non-small-cell lung cancer. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma.
Some of the important mutations include epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in small cell lung cancer, human epidermal growth factor receptor (HER2) mutation in breast cancer, and BRAF mutation in melanoma.
RNA-seq data was downloaded from the Gene Expression Omnibus (GEO) database for pre- and post-treatment tumor samples from three melanoma patients with EGFR-activating BRAF V600E mutations, and from The Cancer Genome Atlas (TCGA) melanoma database for tumor and non-tumor samples from patients with the BRAF V600E mutation and unknown EGFR activation status.
The US FDA approved a liquid biopsy test for EGFR activating mutations in patients with non-small cell lung cancer (NSCLC) as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFRT790M in NSCLC. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma.
Our preclinical data suggest that EGFR is a potential target in the therapy of BRAF-mutant malignant melanoma; however, more benefits could be expected from irreversible EGFR-TKIs and combined treatment settings.
HER-3 - one of the four member of the tyrosin kinase epidermal growth factor receptors (EGFRs) family- is frequently overexpressed in solid tumors, including melanoma.
We exemplified the applicability of the model using EGFR-gefitinib treatment for Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Cancer (LSCC) and the ERK2-VTX11e treatment for melanoma and colorectal cancer.
Checkpoint inhibitor antibodies have been used for treatment of cutaneous SCC, Merkel cell carcinoma, and MM; epidermal growth factor receptor inhibitors have been used for cutaneous SCC; hedgehog pathway inhibitors have been used for BCC; and BRAF and MEK inhibitors are being used increasingly in the management of MM.
Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, epidermal growth factor receptor (EGFR)-addicted colorectal carcinoma (CRC) DiFi cells and BRAF-addicted CRC COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent.
The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors.
Our findings provide a rationale for why some BRAF or MEK inhibitor-resistant melanoma patients may regain sensitivity to these drugs after a 'drug holiday' and identify patients with EGFR-positive melanoma as a group that may benefit from re-treatment after a drug holiday.
Our results support the hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-Raf(V600E) inhibitor therapy.
Particularly, the mutational status and/or aberrant expression of certain markers, such as EGFR, HER2, cKIT, BRAF and AR, also identified in some tumor histotypes of the salivary glands, currently represent molecular targets for new and efficacious drugs routinely employed in the treatment of other neoplasias, such as breast, lungs, GIST and melanoma.
These assays detect clinically relevant mutations that are correlated with response (BRAF, EGFR) or lack of response (KRAS) to targeted therapies such as selective mutant BRAF inhibitors in malignant melanoma, tyrosine kinases inhibitor in non-small cell lung cancer and anti-EGFR monoclonal antibodies in colorectal cancer, respectively.
Recent evidence suggests that activation of the epidermal growth factor receptor (EGFR)/erbB signaling pathway may be responsible for the development of BRAF inhibitor resistance in melanoma patients.
Thirteen clinical samples (8 lung adenocarcinomas, 3 colon carcinomas and 2 malignant melanomas) already genotyped for EGFR, KRAS and BRAF mutations by current standard-of-care methods (Sanger Sequencing and q-PCR), were analysed for detection of mutations in the same three genes using two NGS platforms and an additional 43 genes with one of these platforms.