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GENE:

KAT6B (Lysine Acetyltransferase 6B)

News alerts, weekly reports and conference planners

KAT6 inhibitors under investigation for solid tumors: the preclinical and early phase progress. (PubMed, Expert Opin Investig Drugs)

Prifetrastat in combination with Fulvestrant is now being evaluated in a phase III trial for pretreated ER+ advanced breast cancer. Additionally, mitigation strategies for dysgeusia and clinically available response-predictive biomarkers should be developed. KAT6 inhibitors with different target spectra, including KAT6A-selective and KAT6/7 inhibitors, may exhibit differential efficacy and safety profiles, offering deeper insights into KAT6-targeted therapy.

6 days ago

Preclinical • Journal

ER (Estrogen receptor) • KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

ER positive

fulvestrant • prifetrastat (PF-07248144)

28d

Phf6 truncating mutation drives leukemogenesis via disrupted epigenetic regulation in mice. (PubMed, Leukemia)

Treatment with CTx-648, a KAT6A/KAT6B inhibitor, restored HSC function in Phf6R274XTg mice and prolonged the survival of leukemic Phf6R274XTg mice. These findings demonstrate a gain-of-function effect for truncated PHF6aa1-273 in driving leukemogenesis and highlight KAT6B as a promising therapeutic target in PHF6 truncation-associated hematologic malignancies.

28 days ago

Preclinical • Journal

PHF6 (PHD Finger Protein 6) • KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

CTx-648

3ms

Lysine Acetyltransferase 6 in Health and Disease. (PubMed, MedComm (2020))

In this review, we summarize the currently available information regarding the physiological and pathological functions of KAT6A and KAT6B and discuss their potential as antitumor targets in drug development. We also present the discovery and development of an emerging class of KAT6 inhibitors under investigation for breast cancer, along with potential molecular mechanisms underlying the therapeutic efficacy of targeting KAT6, providing references for developing therapeutic strategies in clinical practice.

3 months ago

Review • Journal

KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

3ms

Landscape of gene fusions in hormone receptor-positive breast cancer reveals ADK fusions as drivers of progression and potential therapeutic targets. (PubMed, Cell Discov)

Functionally, the most commonly occurring ADK fusion gene, KAT6B::ADK, enhances metastatic potential and confers tamoxifen resistance...Notably, patient-derived organoids harboring KAT6B::ADK from HR+/HER2‒ breast cancer demonstrate increased sensitivity to ADK inhibitors, underscoring the therapeutic potential of this fusion gene. Our findings establish ADK fusions as therapeutic targets in HR+/HER2‒ breast cancer, offering new avenues for innovative precision treatment strategies in this patient population.

3 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KAT6B (Lysine Acetyltransferase 6B)

HR positive • HER-2 negative

tamoxifen

4ms

Oncostatin M induces epigenetic reprogramming in renal cell carcinoma-associated endothelial cells. (PubMed, Commun Biol)

H3K14ac-modified chromatins upregulate specific gene sets associated with hypoxic response, hyper-angiogenesis, inflammation, and mesenchymal transition. Targeting H3K14ac in endothelial cells by interfering with acetyltransferase 6B function or neutralizing Oncostatin M ameliorates the premalignant hyperplastic phenotypes in the autochthonous ccRCC mouse model and diminishes tumor growth and metastasis in the ccRCC xenograft model.

4 months ago

Journal

CA9 (Carbonic anhydrase 9) • KAT6B (Lysine Acetyltransferase 6B)

7ms

Novel kinase-activating genetic events in non-small cell lung carcinomas. (PubMed, Explor Target Antitumor Ther)

ROS1, LTK, and FGFR4 high-level overexpression was observed in 1 out of 89 tumors each. This study demonstrates the scarcity of yet unknown kinase-activating alterations in NSCLCs.

7 months ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • FGFR4 (Fibroblast growth factor receptor 4) • LTK (Leukocyte Receptor Tyrosine Kinase) • RPS6KB1 (Ribosomal Protein S6 Kinase B1) • CLIP1 (CAP-Gly Domain Containing Linker Protein 1) • KAT6B (Lysine Acetyltransferase 6B) • VMP1 (Vacuole Membrane Protein 1)

8ms

Lysine Acetyltransferase 6 Complexes in Neurodevelopmental Disorders and Different Types of Cancer. (PubMed, Results Probl Cell Differ)

The evolutionary conservation of these complexes in Drosophila melanogaster and Caenorhabditis elegans underscores their fundamental biological significance. Understanding the structural and functional mechanisms of KAT6-BRPF1 complexes provides insight into their pathological roles and therapeutic potential.

8 months ago

Journal

KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

8ms

Bromodomain and PHD Finger-Containing Protein 1: From Functions to a Developmental Disorder, Cancer, and Therapeutics. (PubMed, Results Probl Cell Differ)

This review provides a brief overview of BRPF1 and its contribution to the molecular structure and biological functions of KAT6A and KAT6B complexes. We will explore the emerging evidence linking BRPF1 dysfunction to human diseases, particularly cancer and abnormal neurodevelopment, to highlight promising therapeutic opportunities for treating associated pathology.

8 months ago

Journal

KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

8ms

Inhibition of circ_0127646 Enhanced the Cisplatin Sensitivity in Osteosarcoma Cells via miR-22/KAT6B Axis. (PubMed, J Biochem Mol Toxicol)

Collectively, our findings indicated that inhibition of circ_0127646 could enhance the chemosensitivity of OS cells to cisplatin via miR-22/KAT6B axis. Circ_0127646 might serve as a prognostic biomarker for cisplatin-based therapies and a potential therapeutic target in OS.

8 months ago

Journal

S100A8 (S100 Calcium Binding Protein A8) • S100A9 (S100 Calcium Binding Protein A9) • KAT6B (Lysine Acetyltransferase 6B) • MIR22 (MicroRNA 22)

cisplatin

8ms

Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia. (PubMed, Cancer Discov)

Here we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in range of AML models showing that although KAT6A/B inhibition is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, markedly increases efficacy...Combined inhibition rapidly evicts the MLL-FP from chromatin, potently represses oncogenic transcription and overcomes primary resistance to Menin inhibitors. Notably, KAT7 remains an important targetable dependency in acquired genetic/non-genetic resistance to Menin inhibition providing the molecular rationale for rapid clinical translation of combination therapy, particularly in MLL-FP AML.

8 months ago

Preclinical • Journal

KAT6A (Lysine Acetyltransferase 6A) • KAT6B (Lysine Acetyltransferase 6B)

CTx-648

1year

THE RARE GYNECOLOGIC SARCOMA (REGYS) STUDY. MOLECULAR AND CLINICOPATHOLOGICAL RESULTS OF A PROJECT ON 379 UTERINE SARCOMAS. (PubMed, Lab Invest)

The molecular testing showed that LG-ESS harbor a recurrent fusion in 75.9% and HG-ESS in 43.7% of cases. The results of our study emphasize the diagnostic, prognostic, and predictive significance of molecular testing in mesenchymal uterine tumors.

1 year ago

Journal

NTRK (Neurotrophic receptor tyrosine kinase) • KAT6B (Lysine Acetyltransferase 6B)

NTRK fusion