Researchers from Royal College of Surgeons in Ireland (RCSI) have created a new orthotopic preclinical model of glioblastoma (GBM), designed to recapitulate patient response to standard-of-care and targeted treatments.
Researchers from Adcentrx Therapeutics Inc. recently reported preclinical data for the Nectin-4-targeting antibody-drug conjugate (ADC) ADRX-0706, currently in phase I development for the treatment of solid tumors (NCT06036121).
Son of sevenless homolog 1 (SOS1) plays a crucial role in the conversion of KRAS from its GDP- to its GTP-bound form independently of KRAS mutational status, thus being a promising therapeutic target for all tumors driven by KRAS. Haihe Biopharma Co. Ltd. has presented a potent SOS1 inhibitor, HH-100937, that has been found effective as monotherapy or when combined with drugs targeting the KRAS/MAPK pathway.
The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.
Crossfire Oncology BV has disclosed CFON-026, a potent, highly selective and macrocyclic noncovalent inhibitor of wild-type (WT) Bruton tyrosine kinase (BTK) and all clinically relevant BTK resistance mutations, with best-in-class potential for the treatment of cancer.
Researchers from Dong-A Socio Holdings Co. Ltd. presented a first-in-class Src homology 2 domain-containing phosphatase 1 (SHP1) allosteric inhibitor, SB-8091, being developed as an anticancer agent.
Rac1 is a small GTPase, the hyperactivation of which is linked to tumor progression and drug resistance. The oncogenic variant Rac1b has been shown to be overexpressed in cancers, such as colorectal cancer (CRC), and it has also been correlated with poor prognosis and CRC resistance to oxaliplatin.
In tumors with amino acid deprivation, eIF-2α kinase GCN2 is activated and triggers a signaling response to promote cell survival and proliferation. This is important in high metabolically active hematological cancers, such as acute myeloid leukemia (AML).
AR-V7 is the most clinically relevant androgen receptor (AR) splice variant associated with endocrine resistance and poor prognosis in patients with prostate cancer.
Researchers from Zhuhai Grit Biotechnology Co. Ltd. recently presented preclinical characterization of a new genetically modified tumor-infiltrating lymphocyte (TIL) product, GT-216, being developed for the treatment of solid tumors.
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