Cancer Therapeutics
Recent submissions
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Targeting radioresistance and replication fork stability in prostate cancer.
(AMER SOC CLINICAL INVESTIGATION INC, 2022-05-09)The bromodomain and extraterminal (BET) family of chromatin reader proteins bind to acetylated histones and regulate gene expression. The development of BET inhibitors (BETi) has expanded our knowledge of BET protein ... -
Prostate Specific Membrane Antigen Expression and Response to DNA Damaging Agents in Prostate Cancer.
(American Association for Cancer Research (AACR), 2022-05-12)PURPOSE: Prostate specific membrane antigen (PSMA) targeting therapies such as Lutetium-177 (177Lu)-PSMA-617 are impacting outcomes from metastatic castration-resistant prostate cancer (mCRPC). However, a significant subset ... -
Minimal Residual Disease After Autologous Stem-Cell Transplant for Patients With Myeloma: Prognostic Significance and the Impact of Lenalidomide Maintenance and Molecular Risk.
(American Society of Clinical Oncology (ASCO), 2022-04-04)PURPOSE: Minimal residual disease (MRD) can predict outcomes in patients with multiple myeloma, but limited data are available on the prognostic impact of MRD when assessed at serial time points in the context of maintenance ... -
Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.
(Elsevier BV, 2022-04-28)BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have ... -
Precision-Cut Tumor Slices (PCTS) as an Ex Vivo Model in Immunotherapy Research.
(MDPI AG, 2022-04-06)Precision-cut tumor slices (PCTS) have recently emerged as important ex vivo human tumor models, offering the opportunity to study individual patient responses to targeted immunotherapies, including CAR-T cell therapies. ... -
Indisulam targets RNA splicing and metabolism to serve as a therapeutic strategy for high-risk neuroblastoma.
(2022-03-16)Neuroblastoma is the most common paediatric solid tumour and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be ... -
A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer.
(2022-03-22)<h4>Background</h4>miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact ... -
Genome-Protective Topoisomerase 2a-Dependent G2 Arrest Requires p53 in hTERT-Positive Cancer Cells.
Topoisomerase 2a (Topo2a)-dependent G2 arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this arrest is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. ... -
Encoding BRAF Inhibitor Functions in Protein Degraders
<jats:p>Various BRAF kinase inhibitors were developed to treat cancers carrying the BRAF<jats:sup>V600E</jats:sup> mutation. First-generation BRAF inhibitors could lead to paradoxical activation of the MAPK pathway, limiting ... -
Individualised prediction of drug response and rational combination therapy in NSCLC using artificial intelligence enabled studies of acute phosphoproteomic changes.
(2022-04-03)We hypothesise the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed ... -
Presence of human breast cancer xenograft changes the diurnal profile of amino acids in mice.
(2022-01-19)Human xenografts are extremely useful models to study the biology of human cancers and the effects of novel potential therapies. Deregulation of metabolism, including changes in amino acids (AAs), is a common characteristic ... -
New Fully Automated Preparation of High Apparent Molar Activity <sup>68</sup>Ga-FAPI-46 on a Trasis AiO Platform.
(2022-01-20)A large number of applications for fibroblast activation protein inhibitors (FAPI)-based PET agents have been evaluated in conditions ranging from cancer to non-malignant diseases such as myocardial infarction. In particular, ... -
Dual blockade of the PI3K/AKT/mTOR (AZD8055) and RAS/MEK/ERK (AZD6244) pathways synergistically inhibits rhabdomyosarcoma cell growth in vitro and in vivo.
<h4>Purpose</h4>To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major cause of pediatric and adolescent cancer ... -
Prostate specific membrane antigen and DNA damage repair in advanced prostate cancer
(Institute of Cancer Research (University Of London), 2022-03-31)Identification and implementation of novel therapeutic strategies for advanced prostate cancer (PCa) remains an urgent, unmet clinical need. Prostate Specific Membrane Antigen (PSMA), a PCa biomarker, is currently being ... -
Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant.
(2021-12-29)<h4>Background</h4>Diffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant ... -
Exploiting the CRL4-CRBM E3 ubiquitin ligase complex for the development of iTAG: a versatile targeted protein degradation system to enable functional evaluation and target validation
(Institute of Cancer Research (University Of London), 2022-02-28)Modulating target protein expression to probe for its relevance and function in a disease is critical in the drug discovery process of target validation. Current genetic methods and chemico-biology tools are widely employed ... -
FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas.
(2021-11-30)Rhabdomyosarcomas are aggressive pediatric soft-tissue sarcomas and include high-risk PAX3-FOXO1 fusion-gene-positive cases. Fibroblast growth factor receptor 4 (FGFR4) is known to contribute to rhabdomyosarcoma progression; ... -
Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket.
We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors ... -
HER3 Is an Actionable Target in Advanced Prostate Cancer.
It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that ...
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