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Introduction
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Publications
Publications (37)
Background
Despite the advancements in new therapies for colorectal cancer (CRC), chemotherapy still constitutes the mainstay of the medical treatment. For this reason, new strategies to increase the efficacy of chemotherapy are desirable. Poly-ADP-Ribose Polymerase inhibitors (PARPi) have shown to increase the activity of DNA damaging chemotherape...
A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFβ signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic sp...
Background
RAS mutations are the only validated biomarkers in metastatic colorectal cancer (mCRC) for anti-epidermal growth factor receptor (EGFR) therapy. Limited clinical information is available on AXL expression, marker of epithelial to mesenchymal transition, in mCRC.
Methods
AXL was retrospectively assessed by immunohistochemistry in 307 pat...
Background
Previous studies showed that the combination of an anti-Epidermal growth factor (EGFR) and a MEK-inhibitor is able to prevent the onset of resistance to anti-EGFR monoclonal antibodies in KRAS-wild type colorectal cancer (CRC), while the same combination reverts anti-EGFR primary resistance in KRAS mutated CRC cell lines. However, rapid...
Background:
Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is an effective treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients receive clinical benefits from anti-EGFR therapies, due to the development of resistance...
Background:
Molecular mechanisms driving acquired resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) are complex but generally involve the activation of the downstream RAS-RAF-MEK-MAPK pathway. Nevertheless, even if inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance, its use is limited by the d...
Background
Molecular mechanisms driving acquired resistance to anti-EGFR therapies in metastatic Colorectal Cancer (mCRC) are complex but generally involve the activation of the downstream RAS-RAF-MEK-MAPK pathway.
Methods
In order to understand the mechanism underlying MEK inhibitor (MEKi) resistance, we generated three different MEKi resistant m...
Background
AXL and transforming growth factor β (TGF-β) signalling pathways play a key role in modulating tumour microenvironment by promoting epithelial to mesenchymal transition (EMT), stromal activation and regulating immune response in colorectal cancer (CRC). Here we have evaluated the effect of double blockade of TGF-β and AXL receptors, as a...
Background:
The clinical impact of the monoclonal antibody cetuximab targeting the EGFR in colorectal cancer (CRC) is widely recognized. Nevertheless, the onset of cetuximab resistance is a serious issue that limits the effectiveness of this drug in targeted therapies. Unraveling the molecular players involved in cancer resistance is the first ste...
Many cell stressors block protein translation, inducing formation of cytoplasmic aggregates. These aggregates, named stress granules (SGs), are composed by translationally stalled ribonucleoproteins and their assembly strongly contributes to cell survival. Composition and dynamics of SGs are thus important starting points for identifying critical f...
DNA damage response (DDR) is crucial in a variety of tumors and several new drugs that interfere with this mechanism are already available or in advanced clinical testing. RAS-MAPK pathway activation, induced by either RAS or BRAF mutation, is a frequent feature of colorectal cancers (CRCs) and is strongly associated to mitotic stress and dependenc...
According to the consensus molecular subtypes (CMS), almost 23% of human colorectal cancer (CRC) are classified in the CMS4 group, characterized by a mesenchymal signature and the activation of transforming growth factor β (TGF-β) signaling. AXL is a tyrosine kinase receptor involved in epithelial to mesenchymal transition, angiogenesis and immune...
DNA damage response (DDR) is crucial in a variety of tumors and several new drugs that interfere with this mechanism are already available or in advanced clinical testing. RAS-MAPK pathway activation, induced by either RAS or BRAF mutation, is a frequent feature of colorectal cancers (CRCs) and is strongly associated to mitotic stress and dependenc...
According to the consensus molecular subtypes (CMS), almost 23% of human colorectal cancer (CRC) are classified in the CMS4 group, characterized by a mesenchymal signature and the activation of transforming growth factor β (TGF-β) signaling. AXL is a tyrosine kinase receptor involved in epithelial to mesenchymal transition, angiogenesis and immune...
The EPHA2 tyrosine kinase receptor is implicated in tumor progression and targeted therapies resistance. We evaluated EPHA2 as a potential resistance marker to the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in colorectal cancer. We studied activation of EPHA2 in a panel of human colorectal cancer cell lines sensitive...
Nature Reviews Clinical Oncology, (2017). doi:10.1038/nrclinonc.2017.43 Jason J. Luke 0 0 2017-03-27T13:39:00Z 2017-11-29T14:35:00Z 1 312 1781 14 4 2089 14.0 Normal 0 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:y...
p>Molecular mechanisms driving acquired resistance to anti-EGFR therapies in mCRC is complex and biochemically converge to activate the EGFR-RAS-MAPK pathway. In order to understand the mechanism underlying MEKi resistance, SW48 MEKi resistant cell lines (SW48-MR) have been established by in vivo selection. To expand our results, another CRC cell l...
Introduction
Cetuximab and panitumumab, antibodies directed against the epidermal growth factor receptor (EGFR), are an effective clinical therapy for patients with metastatic colorectal cancer (mCRC), particularly for those with KRAS, NRAS, BRAF and PI3KCA wild-type cancer. However, only a fraction of patients receives clinical benefit from therap...
The human DKC1gene encodes dyskerin, an evolutionarily conserved nuclear protein whose overexpression represents a common trait of many types of aggressive sporadic cancers. As a crucial component of the nuclear H/ACA snoRNP complexes, dyskerin is involved in a variety of essential processes, including telomere maintenance, splicing efficiency, rib...
Purpose
Regorafenib, an oral multikinase inhibitor, has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients that have progressed after all standard therapies. However, novel strategies to improve tolerability and enhance anti-cancer efficacy are needed.
Experimental design
We have evaluated in vitro the effects of regoraf...
Purpose
We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors.
Experimental design
MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study b...
