The Institute of Cancer Research (ICR) in London is shifting the focus of drug discovery from molecular targets in cancer cells to take in the whole ecosystem supporting tumor growth, evolution and the development of resistance. The aim is to exploit new understanding of the way cancers evolve within the ecosystem of the body, the interaction between cancer cells and the immune system, and the reliance of a tumor on the tissue and growth signals that surround it. Manipulating this environment could make cancer cells become “extinct,” ICR researchers say.
A combination of radiation therapy and CD47 blockade induced an abscopal effect in animal studies even in animals that lacked T cells, researchers reported in the Nov. 21, 2022, online issue of Nature Cancer. The findings are “the first demonstration of T-cell-independent abscopal response,” co-corresponding author Edward Graves told BioWorld. “We’re not trying to say that all abscopal responses are macrophage-mediated. There are plenty that require T cells,” Graves clarified. But “there is another avenue of abscopal responses that has not been reported. ... All the abscopal literature is about stimulating an adaptive response.”
Additional early-stage research and drug discovery news in brief, from: Altamira Therapeutics, Lantern Pharma, Marvel Biosciences, Olix Pharmaceuticals.
Wigen Biomedicine Technology (Shanghai) Co. Ltd. has described pyrrolopyrimidine derivatives as Wee1-like protein kinase (Wee-1) inhibitors reported to be useful for the treatment of cancer.
Shanghai Xucheng Pharmatech Co. Ltd. has divulged retinoid acid receptor γ (RARγ) agonists reported to be useful for the treatment of acne, psoriasis, ichthyosis, keratosis, skin hyperpigmentation and dry eye.
Sichuan Haisco Pharmaceutical Co. Ltd. has identified proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety covalently bonded to an EGFR (HER1; erbB1) targeting moiety through a linker reported to be useful for the treatment of non-small-cell lung cancer (NSCLC).
Viva Star Biosciences Ltd. has synthesized lysophosphatidic acid receptor 1 (LPAR1; EDG2) antagonists reported to be useful for the treatment of fibrosis, chronic kidney disease, diabetic nephropathy, nonalcoholic steatohepatitis (NASH), systemic scleroderma (systemic sclerosis) and idiopathic pulmonary fibrosis.
Sitryx Therapeutics Ltd. has disclosed 2-methylene-4-oxo-butanoic acid derivative compounds acting as nuclear factor erythroid 2-related factor 2 (NFE2-related factor 2; NFE2L2; NRF2) activators reported to be useful for the treatment of inflammatory disorders.
The liver X receptor (LXR) is a nuclear hormone receptor that is one of the most important regulators of cholesterol homeostasis and plays a key role in triglyceride (TG) regulation. Researchers from Orsobio Inc. and Phenex Pharmaceuticals AG have presented preclinical data on TLC-2716, a potent, small-molecule LXR inverse agonist for the treatment of lipid disorders.
Subpopulation of senescent-like cells are known contributors to acquiring drug resistance in cancer. Potential therapies are increasingly being developed with designs to reduce the proportion of slowly dividing cells rather than to kill hyperproliferative cells. Insufficient RNA-binding protein HuR/ELAVL1 levels are known to cause cell senescence, while increased HuR is associated with proliferation.