Researchers have found that exposure to secondhand smoke during treatment with cisplatin may reduce its effectiveness in patients with head and neck cancer, even if they don’t have a history of smoking, according to a recent study published by Sadhasivam et al in the International Journal of Molecular Sciences.
Background
Tobacco use is a well-established risk factor for cancer and a signal of poor outcomes, especially in patients who continue to smoke during treatment. However, the effects of secondhand smoke on cancer treatment have been little understood. Estimates suggest than 20% of nonsmoking U.S. adults may be exposed to secondhand smoke. Exposure is highest among Black individuals, those living in poverty, and children aged 3 to 11 years. Secondhand smoke exposure causes over 41,000 deaths among nonsmoking adults and 900 deaths in infants each year.
“Head and neck cancer is the sixth most common cancer [type] worldwide and is prevalent in Oklahoma, where we also have a high rate of smoking. This is the first time that researchers have examined the impact of secondhand smoke exposure on patients [with cancer] and the mechanism of why it is happening. Our studies will continue, but we think it is important to raise awareness now that [patients] who are exposed to secondhand smoke during treatment will likely have a worse prognosis,” stressed senior study author Lurdes Queimado, MD, PhD, Professor of Otolaryngology at the University of Oklahoma College of Medicine and Director of the Tobacco Registry Science Lab in the Tobacco Settlement Endowment Trust Health Promotion Research Center at the Oklahoma University Health Stephenson Cancer Center.
Study Methods and Results
In the recent study, the researchers exposed head and neck cancer cells to secondhand smoke for 48 hours and compared the outcomes with a control group of cancer cells that was not exposed to secondhand smoke. Simultaneously, the cells in both groups were treated with cisplatin.
The researchers discovered that twice as much cisplatin was needed to kill the cells exposed to secondhand smoke vs the cells not exposed to secondhand smoke. In addition, the cancer cells that survived treatment with cisplatin were much more likely to replicate indefinitely.
“This was concerning to discover because not only was the effectiveness of the chemotherapy cut in half, but the cells that survived were able to divide and create huge colonies of cancer cells,” Dr. Queimado emphasized. “If the chemotherapy can’t kill all the cancer, it will come back—and it will come back sooner because the cells are dividing so quickly. In addition, we cannot simply double the amount of chemotherapy we give to patients because it would be too toxic,” she continued.
After exploring how exposure to secondhand smoke decreased the effectiveness of cisplatin, the researchers revealed that secondhand smoke altered the expression of several proteins involved in drug resistance, effectively restricting cisplatin’s ability to kill cancer cells.
“Cisplatin kills cancer cells by binding to their DNA and keeping the cells from dividing, but if cisplatin can’t get into the cell, it’s not going to kill it. Essentially, there are doors to the cancer cells that control how cisplatin gets in and out. In the presence of secondhand smoke, there were fewer doors for cisplatin to enter, and there were many more doors for cisplatin to exit. So, not only is less cisplatin getting into the cell, but more of it is leaving the cell before it has a chance to kill it,” Dr. Queimado explained.
Conclusions
Although cisplatin is the preferred type of chemotherapy for treating head and neck cancer, physicians may want to consider another drug if they know their patients will be exposed to secondhand smoke during treatment. Nonetheless, secondhand smoke exposure may affect other drugs, including noncancer treatments.
“The proteins affected by secondhand smoke are not specific [to] cisplatin; they are involved in resistance to other drugs. We have not studied that yet, but it is likely that secondhand smoke decreases the effectiveness of several types of drugs,” underscored the study authors.
They indicated that the new findings may broaden the significance of smoking cessation during cancer therapy. In addition, their research pointed to the ongoing public health ramifications of both active smoking and exposure to secondhand smoke.
“For patients with tobacco-related cancers, smoking cessation has been shown to improve survival, so it is a part of comprehensive cancer treatment plans. This study provides novel data that would suggest including family members in the smoking cessation plan to reduce secondhand smoke exposure during chemotherapy for head and neck cancer may improve outcomes,” underscored Greg Krempl, MD, Professor and Chair of the Department of Otolaryngology–Head and Neck Surgery at the University of Oklahoma College of Medicine.
“Even though this study was conducted in the laboratory, it closely mimics human exposure to secondhand smoke,” noted lead study author Balaji Sadhasivam, PhD, Assistant Professor of Occupational and Environmental Health at the University of Oklahoma Hudson College of Public Health. “If patients [with cancer] live with someone who smokes, it is important for them to avoid being exposed to smoke while they are being treated. We want to do everything we can to help [patients] have better outcomes from their treatment,” he concluded.
Disclosure: For full disclosures of the study authors, visit mdpi.com.
