Tobacco use is an established risk factor for the development of several cancers; however, far less work has been done to understand the effects of continued smoking on cancer treatment outcomes, and structured tobacco cessation efforts are not well incorporated into the standard care for patients with cancer. In this Review we discuss the known biological effects of smoking on cancer cell biology and emphasise the clinical effects of continued smoking in patients with cancer treated with chemotherapy or radiotherapy. Although evidence supports the need for inclusion of dedicated tobacco cessation efforts for patients with cancer, clinicians should consider the methods used to provide evidence-based tobacco cessation support and the available resources to deliver and maintain consistent tobacco cessation support. We also address the variables to consider in the design and implementation of a sustainable tobacco cessation programme.

Smoking is one of the largest preventable risk factors for developing cancer, and continued smoking by cancer patients is associated with increased toxicity, recurrence, risk of second primary cancer, and mortality. Cigarette smoke (CS) contains thousands of chemicals, including many known carcinogens. The carcinogenic effects of CS are well established, but relatively little work has been done to evaluate the effects of CS on cancer cells. In this review of the literature, the authors demonstrate that CS induces a more malignant tumor phenotype by increasing proliferation, migration, invasion, and angiogenesis and by activating prosurvival cellular pathways. Significant work is needed to understand the biologic effect of CS on cancer biology, including the development of model systems and the identification of critical biologic mediators of CS-induced changes in cancer cell physiology. Cancer 2014;120:3617-26.

Background: The 2014 Surgeon General's Report concludes that cigarette smoke (CS) causes increased cancer specific mortality. Clinical data support that the effects of CS are reversible, but there are no extant biologic models that have shown therapeutic response profiles for cancer cells exposed to CS. Methods: An acute, subacute, and chronic dose escalated CS exposure model was developed to test the hypothesis that CS decreases therapeutic response to chemotherapy (CT, cisplatin) and radiotherapy (RT, 0, 2, 4, and 6 Gy) in a reversible manner in cancer cells. Results: H460, A549, and FaDu cancer cells were treated with single and multiple exposure CS for up to 12 weeks. Subacute and prolonged exposure to CS significantly decreased response to CT and RT. CS increased survival fraction following CT or RT between 30-157% across all cell lines. Exposure of cancer cells to CS for 6 or 9 weeks followed by removal of CS for 3 and 6 weeks resulted in a partial to complete restoration of baseline therapeutic response in a cell specific manner; however, all cell lines required several weeks to achieve a partial or full restoration of therapeutic response. Dose response curves for CS exposure demonstrate that H460 and A549 cells had a decreased therapeutic response profile at higher CS concentrations while FaDu cells were more sensitive to lower concentrations to CS. Dose response curves further demonstrated that high dose CS exposure was cytotoxic in all cell lines. Results were verified in all cell lines using 2 additional repeated experiments with freshly thawed cancer cells purchased from ATCC over 10 months. Conclusions: CS exposure reproducibly decreases therapeutic response to CT and RT in a dose dependent and reversible manner, reflective of clinical observations. Dose specific effects may vary between cancer cells. Data suggest that the biologic effects of CS removal, such as with acute smoking cessation in cancer patients, may not manifest in an immediate restoration of cancer cell response to CT or RT. Citation Format: Graham W. Warren, Michelle Romano, Samantha Sobus, Sundaravadivel Balasubramanian. Cigarette smoke and therapeutic response to chemotherapy and radiotherapy in cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5593. doi:10.1158/1538-7445.AM2015-5593