A5036893022- Lung Cancer Treatments and Mutations
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Thyroid Cancer Diagnosis and Treatment
- Cardiac, Anesthesia and Surgical Outcomes
- Global Health and Surgery
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Lung Cancer Research Studies
- RNA modifications and cancer
- COVID-19 and healthcare impacts
- Breast Lesions and Carcinomas
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- CAR-T cell therapy research
- Breast Cancer Treatment Studies
- Cancer, Hypoxia, and Metabolism
- Chemical Reactions and Isotopes
- Chronic Lymphocytic Leukemia Research
- Colorectal Cancer Screening and Detection
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
Queen's University Belfast
2022
Cancer Research UK Manchester Institute
2016-2020
University of Manchester
2016-2020
A combination of focused library and virtual screening, hit expansion, rational design has resulted in the development a series inhibitors RET
<ns4:p>RET (REarranged during Transfection) is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET mechanism oncogenesis medullary thyroid carcinomas where both germline sporadic activating somatic mutations are prevalent.</ns4:p><ns4:p> At present, there no known specific inhibitors clinical development, although many potent have been opportunistically identified through selectivity...
<ns4:p>RET (REarranged during Transfection) is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET mechanism oncogenesis medullary thyroid carcinomas where both germline sporadic activating somatic mutations are prevalent.</ns4:p><ns4:p> At present, there no known specific inhibitors clinical development, although many potent have been opportunistically identified through selectivity...
Abstract The concept of harnessing the immune system to target cancer cells has been an active area research for decades. advent antibodies targeting checkpoint receptors CTLA-4 and PD-1/PDL-1, have now provided definitive clinical validation this approach. Since these discoveries search small molecule immuno-oncology agents intensified. Here we present data on HPK1 (hematopoietic progenitor kinase 1), a novel involved in negative regulation T-cell receptor (TCR) signalling describe high...
Abstract Activating gene fusions in the RET receptor tyrosine kinase have been found to drive 1-2% of lung adenocarcinomas and therefore offer an attractive target for targeted therapy. Whilst non-selective inhibitors with activity are efficacious this setting, their use is generally limited by dose limiting toxicity associated more potent versus other targets, specifically KDR (VEGFR2) case cabozantinib vandetanib. Given limitation, there considerable interest developing selective kinase....
Abstract Background: The aim of this CRUK-MI Drug Discovery project is to deliver a RET-selective inhibitor for the treatment cancers with RET activating mutations, which include 1-2% lung adenocarcinomas and medullary thyroid (MTC). Recent data supports hypothesis that efficacy vandetanib cabozantinib, clinically approved multi-kinase inhibitors, limited by toxicities associated potent activity against KDR. Therefore, would represent best-in-class agent these cancers. Methods: We have...
Abstract The identification of novel oncology targets for small molecule drug discovery is becoming increasingly challenging despite 10-15% the human genome estimated to be druggable. literature an important source targets; however, several recent reports by pharma and academia have indicated that approximately 11-55% published studies are irreproducible. Moreover, attrition rates extremely poor, with 66% candidates in Phase III clinical trials not achieving approval. This reflected...
Abstract Background: Constitutive activation of RET kinase activity following mutation or rearrangement can lead to the development cancers such as medullary thyroid carcinoma and lung adenocarcinoma. The currently approved therapeutics for these diseases are significantly compromised due dose-limiting toxicities associated with off-target vs KDR (VEGFR2) lack potency anticipated secondary resistance (e.g., gatekeeper) mutations. Consequently there is considerable interest in highly...