Health Science Reviews

By Thobeka Makoaqa

Gastric cancer remains one of the deadliest cancers globally, particularly in its advanced stages where treatment options are limited. Chemotherapy with paclitaxel (PTX) is common, but its effectiveness is often short-lived due to resistance that renders cancer cells unresponsive. However, a promising new development may shift this grim reality. Enter CC48 a novel compound that targets cannabinoid receptor subtype 2 (CB2R) and inhibits the enzyme FAAH, showing powerful potential in overcoming chemotherapy resistance.

According to Schirizzi et al. (2025), CC48 not only suppresses tumor growth in paclitaxel-resistant gastric cancer cells but also amplifies PTX’s effectiveness when used together. This dual-action compound increases cancer cell death (apoptosis) reduces cell proliferation (measured via Ki67 levels), and halts cancer cell migration by targeting epithelial-mesenchymal transition proteins like vimentin.

The aim of the study was to understand how activating the CB2 receptor (CB2R) can help slow the growth and spread of gastric cancer. Researchers tested several compounds, including CC48, which does not only activate CB2R but also block FAAH (an enzyme that breaks down natural cannabinoids), making it a suitable multitarget drugs for improving Gastric cancer treatment.

In laboratory and animal models (female mice), CC48 achieved remarkable results: it significantly reduced tumor volume, promoted autophagy (the cell’s self-cleaning process), and induced activation of key apoptosis markers like caspase 3/7.  Its immunomodulatory effects, such as reducing levels of pro-inflammatory cytokines like IL-12 and G-CSF, further support its therapeutic promise.

the uniqueness of CC48 is discovered through its multitarget approach which engages both CB2R and FAAH to trigger anti-cancer mechanisms. Unlike single-target drugs, CC48 provides a holistic therapeutic strategy, simultaneously addressing inflammation, resistance, and tumor survival.

Reference:

Schirizzi, A., Renna, N., De Leonardis, G., Montanaro, R., et al. (2025). CC48 a new CB2R agonist/FAAH inhibitor dual drug blocks gastric cancer progression and overcomes paclitaxel resistance. Journal of Experimental & Clinical Cancer Research, 44, 209. https://doi.org/10.1186/s13046-025-03476-7