Drugs to treat lung cancer are not very effective and radiation has major side effects, but researchers are finding new ways to tackle both problems.
Small cell lung cancer is one of just a few cancer types for which there are very few treatment options. One of the few options, the chemotherapy drug carboplatin, often helps for a few months and then stops working. Radiation can’t safely be used if the cancer spans both lungs.
But a pair of new studies suggests that more effective drugs and less destructive radiation may both be on the way.
A drug in development at the British pharmaceutical giant AstraZeneca slows tumor growth and hits especially hard-to-reach cells, according to a study at the University of Manchester in the U.K., funded by the drug company and published in the journal Clinical Cancer Research.
Small cell lung cancer grows quickly, and the drug, now called AZD3965, may be able to use cancer’s quick growth against it. Cancer cells disproportionately burn glucose, producing lactate as a waste product. Researchers hope the AstraZeneca drug can interfere with the cells’ ability to get rid of that waste.
“Because they grow so rapidly, and use up energy so quickly so we figured that their altered metabolism might be something we could target,” study author Christopher Morrow told Healthline.
The Manchester work showed that the drug did trip up the process, though only in cells that didn’t have a backup mechanism, called MCT4, to clear out the waste lactate. Roughly one-fifth of patients have tumors that lack MCT4, according to Morrow.
One-fifth of patients is not many, but it is a significant number when it pertains to a deadly condition like small cell lung cancer, which has an overall survival rate five years after diagnosis as low as 5 percent. And separating patients based on which ones are likely to respond to a given treatment is getting easier all the time.
“We’re very keen on looking at circulating tumor cells, so we’re developing [tests] to look based on a blood test whether patients would respond to this drug,” Morrow told Healthline.
When researchers implanted human tumors without MCT4 in mice and then gave the mice the drug, tumor growth slowed.
And the cells hit hardest by AZD3965 were those that are least responsive to other treatments, meaning that the drug could work well in combination with other treatments, including radiation.
Radiation treatment is inexact and can damage healthy tissue surrounding cancerous tumors. Researchers are trying to make the treatment safer.
The procedure is tricky for patients whose cancer is in the lungs, or near other vital organs like the heart. Lung cancer patients treated with X-ray radiation also sometimes develop scarring on the lungs, which can interfere with lung function.
One method being tested, called FLASH, uses short bursts of radiation cycling on and off a thousand times faster than those used in conventional radiation.
French research published today in the journal Science Translational Medicine shows that FLASH is as effective as conventional X-ray radiation but does less damage to healthy tissue and does not cause scarring or fibrosis. The study was conducted on mice implanted with human lung cancer tumors.
Humans and mice respond to radiation in much the same way, and the mouse test is considered the gold standard for research into radiation-induced fibrosis.
Researchers don’t know exactly why FLASH is punishing to tumor tissue but gentle on normal tissue, but it seems to cause less genetic damage to healthy tissue than conventional radiation.
FLASH is an alternative to another new radiation method called proton radiation, which is already in use in human patients. Clinical trials are investigating the effectiveness of proton radiation for lung cancers.
It’s too early to compare the two methods, lead researcher Vincent Favaudon told Healthline. But both will almost certainly share one shortcoming: limited availability.
“There is currently no way to perform FLASH irradiation with the linear electron accelerators used in conventional radiotherapy facilities,” Favaudon said. “It will require a large technological improvement, yet it is feasible from my point of view.”
Neither of these two treatments will be a silver bullet for difficult lung cancers, but they do indicate that researchers are hard at work developing new drug and radiation treatments for patients with small cell and other tough-to-treat lung cancers.