CANCER RESEARCH TECHNOLOGY LIMITED

The present invention provides a computer-implemented method for detecting cell-free DNA (cfDNA), such as circulating tumour DNA, in a DNA-containing sample obtained from a patient, the method comprising: (a) providing loci of interest comprising at least 2 mutation-containing loci representative of a tumour of the patient (“patient-specific loci”); (b) providing sequence data comprising sequence reads of a plurality of polynucleotide fragments from a DNA-containing sample from the patient, wherein said sequence reads span said at least 2 mutation-containing loci of step (a); (c) optionally, performing reads collapsing to group the sequence reads into read families; (d) calculating the mutant allele fraction across some or all of said at least 2 patient-specific loci, optionally wherein the mutant allele fraction is calculated by aggregating mutant reads and total reads; (e) classifying the sample as containing or not containing the target cfDNA based on the calculated mutant allele fraction. Also provided a related methods and systems.

Provided are compounds of the Formula I, and salts, hydrates and solvates thereof: wherein R 1 , R 2 , R 3 and Q 1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and/or a C797S mutation) that confer resistance to existing EGFR inhibitors.

The present invention provides novel drug-inducible degradation tags (degrons), as well as fusion proteins, cells and pharmaceutical compositions comprising the same. Nucleic acid sequences and vectors encoding the novel degrons are also provided. Methods of using the novel degrons, fusion proteins, cells, pharmaceutical compositions, nucleic acid sequences and vectors are also provided herein.

The present invention relates to methods of predicting whether a subject having a cancer or a pre-cancer would benefit from treatment with an immune checkpoint inhibitor, as well as methods for treating subjects determined to be likely to benefit from such treatment.

This invention relates to the expansion of non-haematopoietic tissue-resident γδ T cells in vitro by culturing lymphocytes obtained from non-haematopoietic tissue of humans or non-human animals in the presence of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) and the absence of TCR activation or co-stimulation signals, without any direct contact with stromal or epithelial cells. Methods of non-haematopoietic tissue-resident γδ T cell expansion are provided, as well as populations of non-haematopoietic tissue-resident γδ T cells and uses thereof.

Provided are compounds of the Formula I, and salts and solvates thereof: (I) wherein R 1 , R 2 , R 3 , X 1 , X 2 , X 3 and Z are defined in the specification. The compounds are inhibitors of salt-inducible kinase (SIK), particular SIK2, and are useful in therapy, particularly in the treatment of a proliferative disorder, a benign neoplasm, pathological angiogenesis, an inflammatory disease or condition, a musculoskeletal disease or condition, an autoimmune disease, a haematological disease or condition, a neurological disease or condition, a psychiatric disorder, or a metabolic disorder.

Provided are compounds of the Formula I, and salts, hydrates and solvates thereof: wherein R 1 , V 1 , R N and Q 1 are each as defined in the specification. The compounds are inhibitors of EGFR, including mutated forms of EGFR (for example EGFR comprising a T790M mutation, a deletion in exon 19 (e.g. A740-A750), an exon 20 insertion, a mutation at L858R and/or a C797S mutation) that confer resistance to existing EGFR inhibitors.

The present invention relates to compounds of formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X 1 , X 2 , R 1 , R 2 , R 30 , R 31 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.

The present invention relates to compounds that function as inhibitors of BCL6 (B-cell lymphoma 6) activity. 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.

Provided are compounds of the Formula (I), and salts and solvates thereof: (Formula (I)) wherein R 2 , R 3 , X 1 , L, A, R 6 , R 7 and Z are defined in the specification. The compounds are inhibitors of salt-inducible kinase (SIK), particular SIK2, and are useful in therapy, particularly in the treatment of a proliferative disorder, a benign neoplasm, pathological angiogenesis, an inflammatory disease or condition, a musculoskeletal disease or condition, an autoimmune disease, a haematological disease or condition, a neurological disease or condition, a psychiatric disorder, or a metabolic disorder.