The key facts
- Complexes with two metals (palladium, copper, zinc) were synthesized, influencing antitumor activity
- The complexes outperformed cisplatin in cytotoxicity on colon and lung cancer cell lines
- The complex with two palladium atoms selectively affected cancer cells without harming healthy tissues
A new approach to treating NSCLC with the KRAS mutation
Russian scientists have obtained new palladium compounds for the treatment of non-small cell lung cancer (NSCLC) with a mutation in the KRAS gene — one of the most difficult-to-treat oncological diseases. This was reported to Gazeta.Ru by the Russian Ministry of Science and Higher Education. The KRAS mutation leads to uncontrolled tumor growth. Modern NSCLC therapy usually proceeds in two stages: chemotherapy with platinum-containing drugs that damage the DNA of tumor cells, followed by targeted agents to inhibit the mutated KRAS protein.
Multi-target action and selectivity
Scientists from IONH RAN showed that introducing two metals (palladium, copper, or zinc) into the complex molecule simultaneously makes it possible to influence its antitumor activity. The synthesized complexes demonstrated a higher cytotoxic effect on colon and lung cancer cell lines compared with the traditional drug cisplatin. The complex with two palladium atoms showed high selectivity toward lung cancer cells, selectively affecting cancer cells without touching healthy tissues. The complexes can bind both to DNA and to the mutant KRAS protein, exerting a multi-target action on the cancer cell.
The goal — overcoming resistance
“Our work is aimed at creating fundamentally new multifunctional antitumor drugs. We strive to obtain compounds that do not simply suppress one survival mechanism of a cancer cell, but act on several targets simultaneously. This could become the key to overcoming the resistance that a tumor often develops to existing drugs,” said Marina Uvarova, Candidate of Chemical Sciences and head of the Youth Laboratory of New Antibacterial Coordination Compounds at IONH RAN.
Further plans and study participants
Next, the scientists plan to continue studying the anticancer activity of the obtained complexes in in vivo models, as well as to modify the molecules to increase their selectivity. The work involved specialists from the Kurnakov Institute of General and Inorganic Chemistry of the RAS, the Engelhardt Institute of Molecular Biology of the RAS, the Blokhin National Medical Research Center of Oncology, RTU MIREA, the Nesmeyanov Institute of Organoelement Compounds of the RAS, and Saratov State Medical University.
