Delving into the Latest Updates on Cancer Research UK Cancer Therapeutics Unit with Synapse

Overview

Tags

Immune System Diseases

Hemic and Lymphatic Diseases

Neoplasms

Molecular glue

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Hemic and Lymphatic Diseases	1
Immune System Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Molecular glue	1

Top 5 Target	Count

BCL6(B-cell lymphoma 6 protein)	1

The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived 'evolutionary history'. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract. We found that involucrin, a keratinocyte differentiation marker, was expressed in a high proportion (78%) of breast carcinoma samples and cell lines. Interestingly, tumour samples found to express high levels of involucrin were also shown to express Brk. 1,25-dihydroxyvitamin D3, a known differentiation agent and potential anti-cancer agent, decreased proliferation in the breast cancer cell lines that expressed both involucrin and Brk, whereas the Brk/involucrin negative cell lines tested were less susceptible. In addition, responses to 1,25-dihydroxyvitamin D3 were not correlated with vitamin D receptor expression. These data contribute to the growing body of evidence suggesting that cellular responses to 1,25-dihydroxyvitamin D3 are potentially independent of vitamin D receptor status and provide an insight into potential markers, such as Brk and/or involucrin that could predict therapeutic responses to 1,25-dihydroxyvitamin D3.

02 May 2023·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Machine learning estimation of human body time using metabolomic profiling

Q1 · CROSS-FIELD

Article

Author: Ackermann, Katrin ; Raynaud, Florence I. ; Kayser, Manfred ; Woelders, Tom ; Revell, Victoria L. ; Skene, Debra J. ; Middleton, Benita ; Hut, Roelof A.

Circadian rhythms influence physiology, metabolism, and molecular processes in the human body. Estimation of individual body time (circadian phase) is therefore highly relevant for individual optimization of behavior (sleep, meals, sports), diagnostic sampling, medical treatment, and for treatment of circadian rhythm disorders. Here, we provide a partial least squares regression (PLSR) machine learning approach that uses plasma-derived metabolomics data in one or more samples to estimate dim light melatonin onset (DLMO) as a proxy for circadian phase of the human body. For this purpose, our protocol was aimed to stay close to real-life conditions. We found that a metabolomics approach optimized for either women or men under entrained conditions performed equally well or better than existing approaches using more labor-intensive RNA sequencing-based methods. Although estimation of circadian body time using blood-targeted metabolomics requires further validation in shift work and other real-world conditions, it currently may offer a robust, feasible technique with relatively high accuracy to aid personalized optimization of behavior and clinical treatment after appropriate validation in patient populations.

03 Feb 2023·The Handbook of Medicinal Chemistry

The Discovery of Checkpoint Kinase 1 Inhibitors: From Fragments to Clinical Candidate

Author: Collins, Ian

Selective inhibitors of the DNA damage response Checkpoint Kinase 1 (CHK1) for the treatment of cancer were discovered by a fragment-based approach. Structure-based optimisation with iterative protein crystallography gave well-characterised chemical tool inhibitors, which enabled a better understanding of the biology of CHK1 inhibition and validated new potential clinical contexts. Multi-parameter optimisation identified the candidate drug SRA737, taken forward to clinical development in combinations with chemotherapy and as a single agent. The project involved close partnerships between academic discovery laboratories and biotechnology companies, drawing on national collaborative networks, charitable grants and venture capital funding to progress the joint drug discovery objectives.

100 Deals associated with Cancer Research UK Cancer Therapeutics Unit

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100 Translational Medicine associated with Cancer Research UK Cancer Therapeutics Unit

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Pipeline

Pipeline Snapshot as of 24 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

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3

Other

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

CCT369260 ( BCL6 )	Diffuse Large B-Cell Lymphoma More	Preclinical
CCT-128930 ( Akt-2 )	Neoplasms More	Pending
CCT-251545 ( CDK19 x CDK8 )	Neoplasms More	Pending
DG013A ( ERAP1 )	Autoimmune Diseases More	Pending