Drug combo therapy in mice blocks drug resistance, halts tumor growth (Cheap cyclophosphamide & cisplatin)

Medical Xpress / Washington University School of Medicine / Nature - Cancer Discovery ^ | August 31, 2022 | Valentina Lukinović et al

[ConservativeMind]

An experimental combination of two drugs halts the progression of small cell lung cancer, the deadliest form of lung cancer, according to a study.

One of the drugs, cyclophosphamide, is an outdated chemotherapy drug once used to treat small cell lung cancer. Both kinds of drugs work at first but falter after a few months as the cancer develops resistance. Platinum-based drugs became the standard of care mainly because they cause lesser side effects, but they have not substantially improved prognosis. Today, the typical patient survives less than a year and a half after diagnosis.

Researchers showed that small cell lung cancer cells resist cyclophosphamide by activating a specific repair process, and demonstrated that throwing a wrench into the repair process makes the drug much more effective. The findings suggest a pathway to better therapies for one of the least treatable forms of cancer.

The team discovered that RNF113A is regulated by a protein called SMYD3. Healthy lung tissue has very little SMYD3, which led the researchers to think that knocking it down might target cancerous cells while sparing healthy ones.

The researchers treated the mice with an inhibitor of SMYD3, cyclophosphamide, both or an inactive solution. Inhibiting SMYD3 alone modestly slowed down the growth of the tumors. Cyclophosphamide initially halted the growth of tumors from both patients, but the tumors started to grow again after about two weeks, indicating that they had developed resistance. However, the combination of the two drugs stopped the tumors in their tracks. They did not restart growing for the duration of the experiment.

[ConservativeMind]

Cyclophosphamide costs around $100 a prescription, according to GoodRX.

[ConservativeMind]

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