On Sep 25th, research team from Fudan University published a groundbreaking research paper titled "Self-assembled PROTACs enable protein degradation to reprogram the tumor microenvironment for synergistically enhanced colorectal cancer immunotherapy" in the journal "Bioactive Materials" (impact factor: 18.0).
In colorectal cancer (CRC) research, β-catenin and STAT3 have been identified as key drivers of cancer growth, progression, and immune evasion. Their co-overexpression is strongly associated with poor prognosis in patients. However, current small molecule inhibitors have limited efficacy due to the reciprocal feedback activation between STAT3 and β-catenin.
Inspired by the PROteolysis TArgeting Chimera (PROTAC), researchers have developed a strategy of nanoengineered peptide PROTACs (NP-PROTACs) to simultaneously degrade β-catenin and STAT3. This novel treatment method involves coupling peptide PROTACs with DSPE-PEG via disulfide bonds and self-assembling into nanoparticles, thereby achieving effective degradation of both proteins.
Studies have shown that the dual degradation of β-catenin and STAT3 mediated by NP-PROTACs exhibits a stronger synergistic antitumor effect compared to single-target treatments. This dual-target approach not only inhibits cancer cell growth and progression but also significantly enhances the infiltration of CD103+ dendritic cells and the cytotoxicity of T cells, alleviating the immunosuppressive microenvironment induced by β-catenin/STAT3 in CRC.
The successful application of NP-PROTACs offers a new avenue for cancer therapy. By simultaneously degrading two pathogenic proteins, this strategy has the potential to overcome the limitations of current treatments and provide more effective therapeutic outcomes. As research progresses, NP-PROTACs are expected to become a new hope for the treatment of colorectal cancer and other types of cancer.
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