Secondhand smoke has ‘dramatic’ impact on chemotherapy effectiveness
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Key takeaways:
- Secondhand smoke significantly reduced the ability of cisplatin chemotherapy to kill head and neck cancer cells.
- Secondhand smoke altered proteins that carried cisplatin into the cell and removed it.
Cisplatin chemotherapy may not reach its potential efficacy in individuals with head and neck cancer if they are exposed to secondhand smoke, according to results published in the International Journal of Molecular Sciences.
The cell-line study showed secondhand smoke drastically reduced the ability of cisplatin to kill head and neck cancer cells and increased their ability to reproduce.
“The decrease in cell death is so dramatic that to attain the same viability as the cells not in the presence of secondhand smoke, we need to double the amount of cisplatin,” Lurdes Queimado, MD, PhD, professor at University of Oklahoma Health Sciences Center, told Healio. “That will not be feasible on a patient with cancer because cisplatin is already so toxic.”
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer in the world, according to background information provided by researchers. Cisplatin is part of standard therapy for HNSCC along with other chemotherapy drugs.
Tobacco smoking causes more than 7 million deaths worldwide every year, and more than 20% of nonsmoking adults in the U.S. are exposed to secondhand smoke.
“We know that 16% of the nonsmoking cancer population are exposed to secondhand smoke,” Balaji Sadhasivam, PhD, assistant professor at University of Oklahoma Health Sciences Center, told Healio. “We really want to know what happens to the secondhand smoke exposure during the cancer treatment.”
Researchers subjected human HNSCC cell lines treated with cisplatin to 48 hours of sidestream smoke, which makes up 85% of secondhand smoke and contains “higher levels of nicotine and carcinogens” than mainstream smoke, which active smokers inhale, they wrote. They compared those with control cells only treated with cisplatin.
The cells observed in secondhand smoke got exposed to “the amount of nicotine that has been reported to exist in individuals that live with smokers,” Queimado said.
Secondhand smoke, by itself, did not reduce cell death.
Nevertheless, cells exposed to secondhand smoke had a “significant decrease in cisplatin-induced cell death” (P < .0001) at every time tested between hours 27 and 45, researchers wrote.
Furthermore, secondhand smoke increased clonogenic survival.
“It increases the cancer cells prolonged or indefinite survival capacity,” Sadhasivam said.
“They will be available to cause metastases because they don’t die,” Queimado added. “There will be more mutation, more invasion, more recurrence.”
Researchers examined the reason this occurred and discovered a decrease in the protein that takes cisplatin into the cell and an increase in the protein that removes it.
“These are like doors into the cell,” Queimado said. “You have an entry, and you have exit. Your entry is more closed than usual, so you don’t get as much cisplatin to the cell, but also your exit doors are completely open.”
Queimado and colleagues have already started planning future research, which includes a prospective study on the impact secondhand smoke has on patients, including gathering details on exposure levels and duration of exposure.
“I’m validating these results with animal models,” Sadhasivam said. “Also, I can see the mechanism in which it has been modified, so if I target any particular biomarkers [or]any particular gene, if that is the one that has been altered by these effects, then targeting that gene can reverse the cancer cells to the cisplatin.”
Researchers also believe smoking cessation and information on secondhand smoke needs to be better integrated into cancer care.
Queimado highlighted her group’s previous research on the importance of education, noting response to chemotherapy improves fourfold in patients who quit smoking between the time of diagnosis and start of treatment compared with those who do not.
“Most [centers] have an automatic identifying of patients who smoke and a referral for every single patient to get smoking cessation,” Queimado said. “However, although the referral works really well, the patients do not follow up on the referral. They don’t get there because the patient is overwhelmed. We don’t need to give patients with cancer anything else to do. We need to bring the service to them.”
Her center is actively working to integrate smoking cessation into its overall cancer treatment plan, including a dedicated smoking cessation specialist and treatments available before cancer therapy begins.
“And we want to include the families of those patients because we now know that is also the exposure to secondhand smoke, and not just the fact that the patient is smoking,” Queimado added.
For more information:
Lurdes Queimado, MD, PhD, can be reached at lurdes-queimado@ouhsc.edu.
Balaji Sadhasivam, PhD, can be reached at balaji-sadhasivam@ouhsc.edu.
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