A5035176895- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- CRISPR and Genetic Engineering
- TGF-β signaling in diseases
- Melanoma and MAPK Pathways
- Diabetes Treatment and Management
- Cancer Research and Treatments
- Colorectal Cancer Treatments and Studies
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Renal cell carcinoma treatment
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Health and Medical Research Impacts
- Biomedical Ethics and Regulation
- Synthesis of Tetrazole Derivatives
- Colorectal Cancer Surgical Treatments
- Marine animal studies overview
- French Urban and Social Studies
- Quinazolinone synthesis and applications
Sanofi (France)
2013-2023
Centre d'Écologie Fonctionnelle et Évolutive
2001
Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for development PI3Kβ-specific inhibitors treatment cancers. This paper describes discovery 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) optimization this new series active selective pyrimidone indoline amide inhibitors....
Class IA PI3K pathway activation resulting from PTEN deficiency has been associated with lack of sensitivity melanoma to BRAF kinase inhibitors. Although previous studies have shown synergistic activity when pan-PI3K inhibitors were combined MAPK in the treatment exhibiting concurrent genetic abnormalities, overlapping adverse events patients limit optimal dosing and clinical application. With aim specifically targeting PTEN-deficient cancers minimizing potential for on-target toxicity...
The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. purpose of this study was to find synthetic lethal interactions deficiency novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells harboring altered wild-type SMAD4....
Abstract The PI3K/mTOR pathway is involved in promoting tumor cell proliferation, survival and metastasis. development of new anticancer therapies targeting different components this has been motivated by the identification somatic PIK3CA missense mutations as well high frequency loss negative regulatory proteins such suppressor PTEN. In last case, abnormal activation downstream effectors mediated PI3Kβ. PTEN deficiency also reported to be resistance a variety therapies. preceding findings...
<p>Gene_scoreMageckComparison</p>
<p>Map of the plasmids to express inducible SMAD4 and Cas9</p>
<p>Behavior of sgRNAs targeting essential and nonessential genes in the screen samples.</p>
<p>QCsummary</p>
<p>Short validation screen in plate to validate the top 4 synthetic lethal gene candidates</p>
<p>94 Putative synthetic lethal genes identified in the screen</p>
<p>Determination of RAB10 localization</p>
<p>sgRNAs against RAB10</p>
<p>Validation of RAB10 susceptibility in two additional cell lines.</p>
<p>sgRNAcounts</p>
<p>library preparation primers</p>
<p>S2. Quality check of the CRISPR screen samples.</p>
<p>Proteins level assessment by western blotting</p>
<p>RAB10 essentiality in cells having altered SMAD4 is confirmed by the vitro CRISPR screen database DepMap</p>
<p>sgRNAscoreMageckComparison</p>
<div>Abstract<p>The TGF-β signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions deficiency order novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral sgRNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells...
<div><p>The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions deficiency novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells harboring...
<p>RAB10 essentiality in cells having altered SMAD4 is confirmed by the vitro CRISPR screen database DepMap</p>
<p>Short validation screen in plate to validate the top 4 synthetic lethal gene candidates</p>
<p>94 Putative synthetic lethal genes identified in the screen</p>