Lung cancer is the primary cause of cancer-related mortality worldwide and although improvements in treatment have been achieved over the last few years, long-term survival rates for lung cancer patients remain poor. Therefore, there is an imperative need for molecularly targeted agents that will achieve long-term disease control. Numerous downstream molecular pathways, such as EGF/RAS/RAF/MEK/ERK and PI3K/AKT/mTOR are identified as having a key role in the pathogenesis of various forms of human cancer, including lung cancer. PI3K/AKT/mTOR signal pathway is an important intracellular signal transduction pathway with a significant role in cell proliferation, growth, survival, vesicle trafficking, glucose transport, and cytoskeletal organization. Aberrations in many primary and secondary messenger molecules of this pathway, including mutations and amplifications, are accounted for tumor cell proliferation, inhibition of apoptosis, angiogenesis, metastasis and resistance to chemotherapy-radiotherapy. In this review article, we investigate thoroughly the biological role of PI3K pathway in lung cancer and its contribution in the development of future therapeutic strategies.

BACKGROUND: Despite the established causal relationship between tobacco smoking and cancer, many cancer patients continue to smoke after diagnosis. This partly reflects ignorance of the beneficial effects of smoking cessation, even after diagnosis. The aim of this study was to demonstrate the effects of continuing or quitting smoking in patients with diagnosed cancer. METHODS: The study was based on a review of medical databases (PubMed Central, MEDLINE, Cochrane Library) in the last 30 y. All articles included in the present analysis were in English. RESULTS: In subjects with early-stage lung cancer, continued smoking after diagnosis is associated with an increased risk of all-cause mortality and decreased survival. Research has demonstrated significant differences in actuarial overall survival favoring the non-smoking group among subjects with lung cancer. In subjects with oral cancer, smoking cessation or reduction leads to a significant reduction in mortality. There is also evidence that tobacco smoking aggravates and prolongs radiotherapy-induced complications. Of particular importance is evidence that continued smoking is associated with adverse effects during anti-cancer treatment. Smoking promotes tumor progression and increases resistance to chemotherapy due to nicotine-induced resistance to apoptosis by modulating mitochondrial signaling. Continued smoking is also related to inferior outcomes of treatment with novel targeted therapies such as erlotinib. Smoking in subjects with gastric and lung cancer is also associated with an increased risk of developing second primary tumors. Quitting smoking after lung cancer diagnosis is associated with a better performance status, whereas persistent smokers have worse overall quality of life. Subjects who continue to smoke despite being diagnosed with cancer report more severe pain than subjects who have never smoked and greater pain-related functional impairment. CONCLUSIONS: Continued smoking after cancer diagnosis is related to reduced treatment efficacy and reduced survival, increased risk for second primary malignancies, and deterioration of quality of life.