- The cocktail prevents the repair of tumor cells, preventing them from developing resistance.

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A study in mice shows that combination therapy stops the progression of small cell lung cancer. / Pexels

An experimental combination of drugs stops one of the deadliest lung cancers in mice

Lung cancer is one of the most deadly cancers in the world every year. Fortunately, in recent years scientists are finding more and more treatments that improve the survival of those who suffer from it.

Now, a team of researchers has managed to stop the progression of small cell lung cancer, one of the most lethal types, in animal models (mice), using an experimental combination of two drugs. Thanks to these promising results, the first trials in humans are already being planned.

An old acquaintance

As described in the scientific media Cancer Discovery, one of these drugs, cyclophosphamide, is an old acquaintance in the treatment of small cell lung cancer: however, it had fallen into relative disuse since the 1980s, when it was replaced by alternatives with fewer side effects.

However, one of the main problems with both this drug and its alternatives was that tumors tended to rapidly develop tolerance to the treatments.

This is where the second component of the cocktail comes into play since its objective is precisely to slow down the repair process by which tumor cells acquire resistance to cyclophosphamide.

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Prevent cell repair

It has been known for some time that small cell lung cancer cells express an unusually high amount of a protein called SMYD3. This protein has among its functions the regulation of a mechanism that repairs a specific type of DNA damage. Specifically, this damage is called alkylation damage, and it is what cyclophosphamide causes to cancer cells.

Therefore, the authors theorized that a drug that was capable of inhibiting the expression of the SMYD3 protein should increase the efficacy of cyclophosphamide.

The experiments showed that, while cyclophosphamide by itself worked only temporarily and the SMYD3 inhibitor slowed down tumor growth to some degree, the combination of both drugs succeeded in completely stopping tumor growth. This effect was maintained throughout the duration of the experiment (approximately one month), much longer than the individual treatments.

This approach, therefore, could bring cyclophosphamide back to the front lines, since what seems to be clear is that the drugs that replaced it do not improve its results much: it is currently estimated that they only add between two and six months of life expectancy of the patient, despite being less harmful to the body.

Naturally, this combination of drugs is still in very early stages of development: after all, it has so far only been tested on mice. However, the team is already looking to start phase one clinical trials in humans.

References

Valentina Lukinovic, Simone Hausmann, Gael S. Roth et al. SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-Talk. Cancer Discovery (2022), DOI: https://doi.org/10.1158/2159-8290.CD-21-0205