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Liver cancer is one of the most common types of cancer in the world.
A few days ago, a joint team of Chinese and Dutch scientists published a study in the journal Nature, showing that in patients with advanced liver cancer who are ineffective against lenvatinib, the EGFR inhibitor gefitinib (gefitinib) is combined with The combination of lenvatinib can break the drug resistance of tumors and effectively inhibit the progression of liver cancer
Lenvatinib is an oral multi-kinase inhibitor that can inhibit vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and other kinases
In this paper, the researchers used CRISPR-Cas9-based high-throughput screening technology to find a kinase target that has a synergistic effect with lenvatinib
▲Operation process of high-throughput screening technology based on CRISPR-Cas9 (picture source: reference [1])
The results of the experiment found that knocking out EGFR from the cells significantly increased the sensitivity of tumor cells to lenvatinib
▲The combined use of gefitinib and lenvatinib significantly reduced tumor volume in two different animal models (picture source: reference [1])
Why can inhibiting EGFR increase the sensitivity of hepatocellular carcinoma to lenvatinib? Further studies have found that liver cancer cells will activate the EGFR–PAK2–ERK5 signaling cascade after being treated with lenvatinib
▲The interaction between FGFR and EGFR signaling pathway (picture source: reference [1])
So, how effective is this therapy in clinical trials? The researchers evaluated the effect of this combination therapy in 12 patients with advanced liver cancer who had already received lenvatinib treatment and developed drug resistance
▲Preliminary clinical trial results of gefitinib and lenvatinib (picture source: reference [1])
In recent years, immunotherapy has also achieved breakthroughs in the treatment of hepatocellular carcinoma.
It is worth mentioning that in a mouse model with immune response, the combination of gefitinib and lenvatinib also resulted in increased infiltration of CD8-positive T cells and natural killer cells into tumors, and it has immunosuppressive ability.
Note: The original text has been deleted
Reference materials:
[1] Jin et al.
[2] Smart combination therapy for liver cancer tackles drug resistance.