Impact Therapeutics (Shanghai) Inc. has synthesized nitrogen-containing fused heteroaromatic bicyclic compounds acting as ubiquitin carboxyl-terminal hydrolase 1 (USP1) inhibitors reported to be useful for the treatment of cancer.
Transcode Therapeutics Inc. has received clearance from the FDA to proceed with a first-in-human phase 0 trial of TTX-MC138 in cancer patients with advanced solid tumors. A single dose of radiolabeled TTX-MC138 will be followed by noninvasive PET-MRI to quantify the amount of radiolabeled TTX-MC138 delivered to metastatic lesions.
CSPC Pharmaceutical Group Ltd. announced that it has been granted approval by the National Medical Products Administration (NMPA) to conduct clinical trials in China with its oral small-molecule cyclin-dependent kinase 2/4/6 (CDK2/4/6) inhibitor, SYH-2043. In preclinical studies, SYH-2043 demonstrated good antitumor effects in multiple solid tumor types, especially in breast cancer with intrinsic resistance and acquired resistance against CDK4/6 inhibitors.
Researchers from Scorpion Therapeutics Inc. presented the discovery and preclinical evaluation of a novel mutant-selective, allosteric phosphoinositide 3-kinase α (PI3Kα) inhibitor, STX-478. In vitro, STX-478 showed mutant selectivity, as it selectively inhibited the viability of cell lines with mutations in the PIK3CA kinase domain and helical domain.
Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate used for the treatment of metastatic HER2+ breast cancer that is refractory to anti-HER2 therapy such as T-DM1, however, there is a lack of knowledge on acquired or innate resistance to the drug.
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors, in combination with letrozole or fulvestrant, have been approved for treating hormone receptor-positive breast cancer. Even though the therapy shows benefits in some patients, resistance develops in other treated patients.
Trastuzumab-based chemotherapy has demonstrated clinical benefits in the treatment of HER2+ breast cancer. There is a percentage of patients who do not respond to therapy and have a poorer prognosis than those who respond. To better understand the mechanisms behind trastuzumab resistance, researchers in China studied the role of transcription elongation factor A protein-like 9 (TCEAL9) in resistance to trastuzumab-based chemotherapy in HER+ breast cancer.
Inhibitors of cyclin-dependent kinase 4 (CDK4) and CDK6, such as palbociclib, have significantly improved progression-free survival of several breast cancer types, such as hormone receptor-positive, HER2-negative luminal breast cancers, with about 40% being unresponsive or refractory to therapy; the main cause of resistance is the selection of mutant clones in the target oncoprotein.
