The endocannabinoid system is involved in pain perception, cognition and mood regulation among other functions. The dysregulation in synthesis and degradation of endocannabinoids results in anxiety, depression or degenerative diseases.
KAT2A is a histone acetyltransferase that functions as a transcriptional activator which, together with its paralogue KAT2B, is markedly overexpressed in acute myeloid leukemia (AML) compared to in hematopoietic progenitor cells.
Interleukin-18 (IL-18) is a pro-inflammatory cytokine that modulates innate and adaptive immune responses. Decoy-resistant IL-18, DR-18, from Simcha Therapeutics Inc., is an engineered IL-18 cytokine able to interact with the IL-18 receptor but resistant to IL-18-binding protein (IL18BP), which is a negative regulator of IL-18 signaling, thus overcoming the antitumoral efficacy limitation seen with recombinant IL-18.
Kura Oncology, Inc. and Kyowa Kirin Co. Ltd.’s selective oral menin inhibitor ziftomenib showed encouraging data across multiple studies, the most encouraging of which were in combination with other standard of care therapies in patients with NPM1-mutant and KMT2A-rearranged acute myeloid leukemia.
Cathepsin G (CTSG) is overexpressed and aberrantly localized for antigen presentation on acute myeloid leukemia blasts and stem cells compared to normal hematopoietic progenitors. Earlier this year, Crossbow Therapeutics Inc. announced the nomination of its first development candidate, CBX-250, a TCR-mimetic (TCRm) bispecific T-cell engager (TCE) antibody targeting a CTSG peptide-human leukocyte antigen (pHLA) complex and CD3.
The lack of acute myeloid leukemia-specific antigens is one of the challenges for targeted immunotherapy together with on-target off-tumor toxicities due to the expression of the target in normal myeloid cells. A subset of T cells – Vδ2 T-cells – which represent ~5% of the T-cell population in healthy donors, are seen as part of emerging immunotherapeutic strategies.
In tumoral cells, the modulation of the G1/S phases of cell cycle is destabilized by amplification and high expression of cyclin E (CCNE) or by mutation or loss of retinoblastoma 1 (RB1) gene. Cancer cells meeting these characteristics have been sown to be highly sensitive to cyclin-dependent kinase 2 (CDK2) depletion.
Researchers from Novacyte Therapeutics Co. Ltd. presented preclinical data for NC-18, a novel HER2-targeting antibody drug conjugate (ADC) being developed for the treatment of HER2-positive/expressing advanced solid tumors.
Biohaven Ltd.’s BHV-7000, a selective Kv7.2/7.3 potassium channel activator, is in phase II/III development for the treatment of focal epilepsy, generalized epilepsy, bipolar disorder and major depressive disorder. The company recently presented findings from preclinical testing assessing the candidate’s potential for the treatment of comorbidities associated with epilepsy.
Cyclins and cyclin-dependent kinases (CDKs) regulate the activity of E2F and Rb to drive cell cycle progression. Disrupting this interaction has shown lethality in cancer cells harboring alterations that lead to higher expression of E2F1.
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