Abstract: The present invention relates to Ataxia-Telangiectasia Mutated and Rad3-related protein kinase (ATR) inhibitors for use in methods of treating BAF-complex deficient cancer. The present invention further provides methods for identifying ATR inhibitors for use in the treatment of BAF complex gene mutant or deficient cancers. Medical uses and methods relating to the treatment of synovial sarcoma using ATR inhibitors are also provided.

Abstract: A method of performing diffusion-weighted magnetic resonance imaging is provided. The method includes a step of: using a neural network to filter a diffusion-weighted image of an object acquired by a magnetic resonance imaging scanner, the neural network being programmed to produce an output image from the acquired image. The neural network improves the signal to noise ratio of the output image relative to the acquired image. The neural network, when applied to a synthetic knife-edge image to which Rician noise providing a signal-to-noise ratio of 13 or more is added, forms a curve of normalised values of modulation-transfer-function against frequency which has a higher area thereunder than the area under the corresponding curve of normalised values of modulation-transfer-function against frequency for a reference Gaussian smoothing filter.

Abstract: This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

Abstract: Methods and systems for analysing the cellular composition of a sample are described, comprising: providing an image of the sample in which a plurality of cellular populations are associated with respective signals and classifying a plurality of query cells in the image between a plurality of classes corresponding to respective cellular populations in the plurality of cellular populations. This is performed by providing a query single cell image to an encoder module of a machine learning model to produce a feature vector for the query image, and assigning the query cell to one of the plurality of classes based on the feature vector for the query image and feature vectors produced by the encoder module for each of a plurality of reference single cell images.

Abstract: The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.

Abstract: The disclosure relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein X1 and X5 is each selected from CR1 or N; X2, X3 and X4 is each selected from CR1, CR2 or N, provided at least one of X2, X3 and X4 is CR2 and provided only one of X1, X2, X3, X4 and X5 can be N. R1, R2, R3, R4, R5, L1, L2 and L3 are as defined herein. Compounds according to Formula (I) are pharmacologically effective as lysyl oxidase (LOX) inhibitors and are believed to be useful in the treatment of, for instance, cancer.

Abstract: The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.

Abstract: The present invention provides a method for predicting whether a human subject having breast cancer will be resistant to, or sensitive to, therapy with a cyclin-dependent kinase (CDK) inhibitor, the method comprising: a) measuring the gene expression in a sample obtained from the breast tumour of the patient to obtain a sample gene expression profile of at least the following modules: (i) a luminal vs.

Abstract: The present invention provides a method for predicting the treatment response of a human bladder cancer patient, the method comprising: a) measuring the gene expression of at least 9, at least 10, at least 15, at least 20 or at least 30 of the genes from Group 1 in Table 10 and at least 1, at least 2, at least 3 or at least 5 of the genes from Groups 2-4 in Table 10 in a sample obtained from the bladder tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Related methods and systems are also described. The invention finds particular use in predicting whether a bladder cancer patient is likely to be sensitive to (chemo)radiation therapy.

Abstract: The present invention provides a method for predicting the treatment response of a human gastroesophageal cancer patient, the method comprising: a) measuring the gene expression of at least 3 of the following genes: CDH1, CDK6, COX2, ELOVL5, GATA4, EGFR, TBCEL, FGF7, CDH17, FNBP1, PIP5K1B, TWIST, CD44, MET, CEACAM1, TOX3, GLIPR2, GSTP1, RON, TMEM136, MYB, BRCA2, FGF1, POU5F1, EPR, DPYD, ABL2 and SH3RF1 in a sample obtained from the gastroesophageal tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Also provided are related computer-implemented methods and methods of treatment of gastroesophageal cancer.

Abstract: The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

Abstract: Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof: wherein W, X, Y, Z, x, R1, R2, R3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.

Abstract: An x-ray micro-beam radiation production system is provided having: a source of accelerated electrons, an electron focusing component configured to focus the electrons provided by the source, and a target which produces x-rays when electrons impinge thereon from the source. The electron focusing component is configured to focus the electrons provided by the source such that they impinge at a focal spot having a width ? formed on a surface of the target.

Abstract: This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

Abstract: The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2, R30, R31 and Ring A are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.

Abstract: The present invention provides a medicament for the treatment or prevention of a cell proliferative disorder, the medicament comprising as an active ingredient a compound represented by formula or a pharmaceutically acceptable salt thereof, wherein the medicament is used in such a manner that: (a) said compound or salt is administered twice weekly for 3 weeks, (b) administration of said compound or salt is paused for the following 1 week, and (c) steps (a) and (b) are subsequently repeated at least once.

Abstract: An x-ray micro-beam radiation production system is provided having: a source of accelerated electrons, an electron focusing component configured to focus the electrons provided by the source, and a target which produces x-rays when electrons impinge thereon from the source. The electron focusing component is configured to focus the electrons provided by the source such that they impinge at a focal spot having a width ? formed on a surface of the target.

Abstract: This invention relates to compounds useful as lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family member (LOXL1, LOXL2, LOXL3, LOXL4) inhibitors. In addition there are contemplated pharmaceutical compositions comprising the compounds and the use of the compounds in the treatment of conditions mediated by LOX and LOXL, for example cancer. In particular a LOX inhibitor such as the present compounds may be for use in the treatment of a cancer associated with EGFR. The present invention also contemplates the identification of biomarkers that predict responsiveness to a LOX inhibitor.

Abstract: The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound capable of inhibiting MPS1, wherein: (i) said subject has previously been treated with a CDK4/6 inhibitor; and/or (ii) said breast cancer is resistant to treatment with a CDK4/6 inhibitor.

Abstract: The present invention provides a method of treatment of prostate cancer, comprising administering a therapeutically effective amount of an inhibitor of IL-23 and/or an inhibitor of IL-23R to a mammalian patient in need thereof. The prostate cancer may be castration resistant prostate cancer (CRPC). The inhibitor may, for example, be an anti-IL-23 antibody, such as risankizumab, guselkumab or tildrakizumab. The method of treatment may further comprise administration of androgen deprivation therapy, such as enzalutamide. Also provided is a method of predicting the development of resistance to androgen deprivation therapy (ADT) in a prostate cancer in a mammalian patient and a related screening method.