Editorial
The challenges of lung cancer in China Lung cancer is the leading cause of cancer death worldwide and is responsible for approximately 1.4 million deaths annually.[1-3] In China, lung cancer has replaced liver cancer as the number one cause of death among people with malignant tumors from 2008.[4] According to statistics from the National Office on Tumor Cure and Prevention, about 600,000 people die of lung cancer each year in China. The main forms of lung cancer are small-cell lung carcinoma (SCLC, approximately 15% of all lung cancers) and nonsmall-cell lung carcinoma (NSCLC, approximately 85%). The treatment and diagnosis of lung cancer are major challenges. However, a better understanding of the molecular origins and development of this disease might contribute to improving the survival and life quality of patients. Similar to many other cancers, lung cancer develops following genetic damage to DNA. This genetic damage influences the normal functions of the cell, such as cell proliferation, programmed cell death (apoptosis), and DNA repair.[5] More accumulation of damage leads to higher risk of cancer. Smoking is a major risk factors for lung cancer in China.[4] Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene.[6] Moreover, nicotine appears to depress the immune response to cancerous growths in exposed tissue.[7] In China, appoximately 30% of the world’s cigarettes are consumed by an estimated 350 million smokers.[8] In addition, the passive smokers also share a significantly increased risk of lung cancer. In China, there has been a steady increase in the rate of household second-hand smoke exposure, and the rate of passive smoking among nonsmoking females has increased to 82.5%.[9] In all, the prevalence of smoking in China remains high with 350 million smokers and 740 million passive smokers.[10] Furthermore, smoking rates are increasing in the young population and in females. Thus, in China, how to control tobacco and reduce smoking rates is the first challenge. Nevertheless, not every type of lung cancer is associated to smoke. Lung adenocarcinoma is the most common type in patients who have never smoked.[11] Lung cancer susceptibility and risk also are increased in inherited cancer syndromes caused
by mutations in p53, retinoblastoma (Rb), and other genes, as well as epidermal growth factor receptor (EGFR).[12] In this issue, Chen et al. evaluated the association between pathology type and the expression level of ERCC1, BRCA1, RRM1, TUBB3, STMN1, TOP2A, and EGFR in Chinese patients with NSCLC and found that STMN1 and TOP2A genes’ mRNA expression were higher in squamous lung cell cancer than that in nonsquamous lung cell cancer and ERCC1 gene expression reversed. This study will contribute to understanding the pathogenesis of different type of NSCLC. Despite of that insignificant expression pattern of EGFR between squamous or nonsquamous cancer of NSCLC, mutations, and amplification of EGFR are common in NSCLC. Somatic mutations in the kinase domain of EGFR in lung adenocarcinoma were found in approximately 10% of specimens from patients in America, while it was found in 30–50% of specimens from patients in Asia.[13] In fact, EGFR mutations often activate the EGFRsignaling pathway in the absence of ligand and promote cell proliferation, survival, antiapoptotic signals, angiogenesis, and tumor invasion. [14] Recently, treatments with EGFR-inhibitors have emerged. EGFR-tyrosine kinase inhibitor (TKI) (such as gefitinib or erlotinib) treatment of lung cancer harboring EGFR gene mutation is one of the prototypes of such therapies.[15] Which strategy is better in the management of advanced NSCLCs, if the inhibition of mutated EGFR with TKIs?[16] EGFRTKIs were effective and had particular activity in 15–30% of NSCLC patients, with EGFR mutations being a major advantage; however, resistance sets in after approximately one year of treatment and remains as one of the biggest obstacles in anticancer treatments.[16] Moreover, there might be a severe dermatologic adverse effect related with gefitinib. In this issue, a case is reported by Li et al. Therefore, the novel therapeutic methods or targets need to be refined or discovered. In this issue, the protein kinase C (PKC) family is being discussed and reviewed as a promising target in lung cancer. The regulation role of PKCs in lung cancer is becoming increasingly clear. And the authors suggest that inhibitors of certain PKC isoforms could be applied in combination with chemo- and radio-therapies to improve therapy effectiveness and repress side-effects. Additionally,
Journal of Cancer Research and Therapeutics - Supplement 2 - 2013 - Volume 9
Qian Liu, Qinghua Zhou Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China For correspondence: Prof. Qinghua Zhou, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. E-mail: zhouqinghua@ lungca.org
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.119098 PMID: **** Quick Response Code:
S65
Liu and Zhou: The challenges of lung cancer in China
the signal transducer and activator of transcription 3 (STAT3) was also involved in the EGFR signaling pathway. STAT3 per se is an important mediator in the progression of lung cancer, which is also reviewed in this issue. The authors suggest that cell competition may be the important contribution that activation of STATs has to tumorigenesis. However, this presumption needs to be confirmed in the future. Considering that the molecular pathogenesis of lung cancer is not clear enough, the development of novel therapies is still a challenge. Comparably, the new strategies in diagnostics, including personalized diagnostics, also depend on the development of the pathogenesis. Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the person’s performance status. Common treatments include surgery, chemotherapy, and radiation therapy. In this issue, two articles focus on the methods of surgery. Ma et al. compared lobe-specific mediastinal lymphadenectomy (LL) and systematic mediastinal lymphadenectomy (SL) for clinical stage T 1aN 0M 0 NSCLC and found that LL has similar efficacy as SL and it was unnecessary to perform systematic lymphadenectomy in such patients. Zhang et al. found that the thoracoscopic anatomic segmentectomy was safe and effective for stage IA peripheral lung cancer. In fact, the prognosis of lung cancer is poor, since it has often metastasized to distant organs.[17] The prognoses of these patients with metastasis lung cancer are usually poor due to the impossibility of complete resection of lung cancer. Jin et al. introduced a single institution experience with pleuropneumonectomy, which might enhance postoperative combined therapy, and beneficial to patients’ long-term survival. Indeed, the mechanism of metastasis of lung cancer is unmet currently. Considering that the consequence of chemotherapy and radiotherapy is still disappointing, it is urgent to elucidate thoroughly the underlying molecular mechanisms of metastasis, which will help provide enough potential targets for clinical applications. Not surprisingly, this research field is the hotspot. Epithelia-mesenchymal transition (EMT) has been widely accepted as the early stage of tumor metastasis.[5] In this issue, the function of histone acetylation and cell polarity during EMT in lung cancer were reviewed by Zhang et al. and Liu et al., respectively. The two reviews give some new perspectives on EMT regulation. Understanding the genetic background of metastasis will contribute to the personalized treatment.[18] Besides, it also assists to finding the molecular predictors of systemic chemotherapy efficacy. In fact, no biomarker has yet reached a level of evidence to allow its routine use in metastatic lung cancer. Consequently, one of the main challenges in the future is to facilitate efficient and personalized therapeutic management of lung cancer, especially metastatic lung cancer.
S66
As molecular mechanisms have been explored in lung cancer more recently, the personalized approach is emerging. Exact characterization and classification to patients with lung cancer will benefit to the specific and efficient management, which will contribute to improve survival rates. However, many challenges exist currently, especially in China, as the factors from environment and genetics are complicated. REFERENCES 1. Herbst RS, Heymach JV, Lippman SM. Lung Cancer. N Engl J Med 2008;359:1367-80. 2. Chen W, Zheng R, Zhang S, Zou X, Zhao P, He J. Lung cancer incidence and mortality in China, 2009. Thorac Cancer 2013;4:102-8. 3. Chen WQ, Zheng RS, Zeng HM. Bayesian age-period-cohort prediction of lung cancer incidence in China. Thorac Cancer 2011;2:149-55. 4. She J, Yang P, Hong Q, Bai C. Lung cancer in China: Challenges and interventions. Chest 2013;143:1117-26. 5. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74. 6. Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 2003;3:733-44. 7. Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002;2:372-7. 8. Fang X, Wang X, Bai C. COPD in China: The burden and importance of proper management. Chest 2011;139:920-9. 9. Han JX, Ma L, Zhang HW, Liu X, Zheng SH, Gan DK, et al. A cross sectional study of passive smoking of non-smoking women and analysis of influence factors on women passive smoking. Wei Sheng Yan Jiu 2006;35:609-11. 10. Zhang J, Ou JX, Bai CX. Tobacco smoking in China:prevalence, disease burden, challenges and future strategies. Respirology 2011;16:1165-72. 11. Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ. Lung cancer in never smokers--a review. Eur J Cancer 2012;48:1299-311. 12. Feldser DM, Kostova KK, Winslow MM, Taylor SE, Cashman C, Whittaker CA, et al. Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature 2010;468:572-5. 13. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in nonsmall-cell lung cancer. J Clin Oncol 2007;25:587-95. 14. Liu Y, He W, Long J, Pang F, Xian L, Chen M, et al. Natural selection and functional diversification of the epidermal growth factor receptor EGFR family in vertebrates. Genomics 2013;101:318-25. 15. Uribe P, Gonzalez S. Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: Molecular bases for EGFRtargeted therapy. Pathol Res Pract 2011;207:337-42. 16. Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A, et al. EGFR-targeted therapy for non-small cell lung cancer: Focus on EGFR oncogenic mutation. Int J Med Sci 2013;10:320-30. 17. Li B, Wang C, Zhang Y, Zhao XY, Huang B, Wu PF, et al. Elevated PLGF contributes to small-cell lung cancer brain metastasis. Oncogene 2013;32:2952-62. 18. Salgia R, Hensing T, Campbell N, Salama AK, Maitland M, Hoffman P, et al. Personalized treatment of lung cancer. Semin Oncol 2011;38: 274-83. Cite this article as: Liu Q, Zhou Q. The challenges of lung cancer in China. J Can Res Ther 2013;9:65-6. Source of Support: Nil, Conflict of Interest: No.
Journal of Cancer Research and Therapeutics - Supplement 2 - 2013 - Volume 9
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
The challenges of lung cancer in China Lung cancer is the leading cause of cancer death worldwide and is responsible for approximately 1.4 million deaths annually.[1-3] In China, lung cancer has replaced liver cancer as the number one cause of death among people with malignant tumors from 2008.[4] According to statistics from the National Office on Tumor Cure and Prevention, about 600,000 people die of lung cancer each year in China. The main forms of lung cancer are small-cell lung carcinoma (SCLC, approximately 15% of all lung cancers) and nonsmall-cell lung carcinoma (NSCLC, approximately 85%). The treatment and diagnosis of lung cancer are major challenges. However, a better understanding of the molecular origins and development of this disease might contribute to improving the survival and life quality of patients. Similar to many other cancers, lung cancer develops following genetic damage to DNA. This genetic damage influences the normal functions of the cell, such as cell proliferation, programmed cell death (apoptosis), and DNA repair.[5] More accumulation of damage leads to higher risk of cancer. Smoking is a major risk factors for lung cancer in China.[4] Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene.[6] Moreover, nicotine appears to depress the immune response to cancerous growths in exposed tissue.[7] In China, appoximately 30% of the world’s cigarettes are consumed by an estimated 350 million smokers.[8] In addition, the passive smokers also share a significantly increased risk of lung cancer. In China, there has been a steady increase in the rate of household second-hand smoke exposure, and the rate of passive smoking among nonsmoking females has increased to 82.5%.[9] In all, the prevalence of smoking in China remains high with 350 million smokers and 740 million passive smokers.[10] Furthermore, smoking rates are increasing in the young population and in females. Thus, in China, how to control tobacco and reduce smoking rates is the first challenge. Nevertheless, not every type of lung cancer is associated to smoke. Lung adenocarcinoma is the most common type in patients who have never smoked.[11] Lung cancer susceptibility and risk also are increased in inherited cancer syndromes caused
by mutations in p53, retinoblastoma (Rb), and other genes, as well as epidermal growth factor receptor (EGFR).[12] In this issue, Chen et al. evaluated the association between pathology type and the expression level of ERCC1, BRCA1, RRM1, TUBB3, STMN1, TOP2A, and EGFR in Chinese patients with NSCLC and found that STMN1 and TOP2A genes’ mRNA expression were higher in squamous lung cell cancer than that in nonsquamous lung cell cancer and ERCC1 gene expression reversed. This study will contribute to understanding the pathogenesis of different type of NSCLC. Despite of that insignificant expression pattern of EGFR between squamous or nonsquamous cancer of NSCLC, mutations, and amplification of EGFR are common in NSCLC. Somatic mutations in the kinase domain of EGFR in lung adenocarcinoma were found in approximately 10% of specimens from patients in America, while it was found in 30–50% of specimens from patients in Asia.[13] In fact, EGFR mutations often activate the EGFRsignaling pathway in the absence of ligand and promote cell proliferation, survival, antiapoptotic signals, angiogenesis, and tumor invasion. [14] Recently, treatments with EGFR-inhibitors have emerged. EGFR-tyrosine kinase inhibitor (TKI) (such as gefitinib or erlotinib) treatment of lung cancer harboring EGFR gene mutation is one of the prototypes of such therapies.[15] Which strategy is better in the management of advanced NSCLCs, if the inhibition of mutated EGFR with TKIs?[16] EGFRTKIs were effective and had particular activity in 15–30% of NSCLC patients, with EGFR mutations being a major advantage; however, resistance sets in after approximately one year of treatment and remains as one of the biggest obstacles in anticancer treatments.[16] Moreover, there might be a severe dermatologic adverse effect related with gefitinib. In this issue, a case is reported by Li et al. Therefore, the novel therapeutic methods or targets need to be refined or discovered. In this issue, the protein kinase C (PKC) family is being discussed and reviewed as a promising target in lung cancer. The regulation role of PKCs in lung cancer is becoming increasingly clear. And the authors suggest that inhibitors of certain PKC isoforms could be applied in combination with chemo- and radio-therapies to improve therapy effectiveness and repress side-effects. Additionally,
Journal of Cancer Research and Therapeutics - Supplement 2 - 2013 - Volume 9
Qian Liu, Qinghua Zhou Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China For correspondence: Prof. Qinghua Zhou, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. E-mail: zhouqinghua@ lungca.org
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.119098 PMID: **** Quick Response Code:
S65
Liu and Zhou: The challenges of lung cancer in China
the signal transducer and activator of transcription 3 (STAT3) was also involved in the EGFR signaling pathway. STAT3 per se is an important mediator in the progression of lung cancer, which is also reviewed in this issue. The authors suggest that cell competition may be the important contribution that activation of STATs has to tumorigenesis. However, this presumption needs to be confirmed in the future. Considering that the molecular pathogenesis of lung cancer is not clear enough, the development of novel therapies is still a challenge. Comparably, the new strategies in diagnostics, including personalized diagnostics, also depend on the development of the pathogenesis. Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the person’s performance status. Common treatments include surgery, chemotherapy, and radiation therapy. In this issue, two articles focus on the methods of surgery. Ma et al. compared lobe-specific mediastinal lymphadenectomy (LL) and systematic mediastinal lymphadenectomy (SL) for clinical stage T 1aN 0M 0 NSCLC and found that LL has similar efficacy as SL and it was unnecessary to perform systematic lymphadenectomy in such patients. Zhang et al. found that the thoracoscopic anatomic segmentectomy was safe and effective for stage IA peripheral lung cancer. In fact, the prognosis of lung cancer is poor, since it has often metastasized to distant organs.[17] The prognoses of these patients with metastasis lung cancer are usually poor due to the impossibility of complete resection of lung cancer. Jin et al. introduced a single institution experience with pleuropneumonectomy, which might enhance postoperative combined therapy, and beneficial to patients’ long-term survival. Indeed, the mechanism of metastasis of lung cancer is unmet currently. Considering that the consequence of chemotherapy and radiotherapy is still disappointing, it is urgent to elucidate thoroughly the underlying molecular mechanisms of metastasis, which will help provide enough potential targets for clinical applications. Not surprisingly, this research field is the hotspot. Epithelia-mesenchymal transition (EMT) has been widely accepted as the early stage of tumor metastasis.[5] In this issue, the function of histone acetylation and cell polarity during EMT in lung cancer were reviewed by Zhang et al. and Liu et al., respectively. The two reviews give some new perspectives on EMT regulation. Understanding the genetic background of metastasis will contribute to the personalized treatment.[18] Besides, it also assists to finding the molecular predictors of systemic chemotherapy efficacy. In fact, no biomarker has yet reached a level of evidence to allow its routine use in metastatic lung cancer. Consequently, one of the main challenges in the future is to facilitate efficient and personalized therapeutic management of lung cancer, especially metastatic lung cancer.
S66
As molecular mechanisms have been explored in lung cancer more recently, the personalized approach is emerging. Exact characterization and classification to patients with lung cancer will benefit to the specific and efficient management, which will contribute to improve survival rates. However, many challenges exist currently, especially in China, as the factors from environment and genetics are complicated. REFERENCES 1. Herbst RS, Heymach JV, Lippman SM. Lung Cancer. N Engl J Med 2008;359:1367-80. 2. Chen W, Zheng R, Zhang S, Zou X, Zhao P, He J. Lung cancer incidence and mortality in China, 2009. Thorac Cancer 2013;4:102-8. 3. Chen WQ, Zheng RS, Zeng HM. Bayesian age-period-cohort prediction of lung cancer incidence in China. Thorac Cancer 2011;2:149-55. 4. She J, Yang P, Hong Q, Bai C. Lung cancer in China: Challenges and interventions. Chest 2013;143:1117-26. 5. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74. 6. Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 2003;3:733-44. 7. Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002;2:372-7. 8. Fang X, Wang X, Bai C. COPD in China: The burden and importance of proper management. Chest 2011;139:920-9. 9. Han JX, Ma L, Zhang HW, Liu X, Zheng SH, Gan DK, et al. A cross sectional study of passive smoking of non-smoking women and analysis of influence factors on women passive smoking. Wei Sheng Yan Jiu 2006;35:609-11. 10. Zhang J, Ou JX, Bai CX. Tobacco smoking in China:prevalence, disease burden, challenges and future strategies. Respirology 2011;16:1165-72. 11. Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ. Lung cancer in never smokers--a review. Eur J Cancer 2012;48:1299-311. 12. Feldser DM, Kostova KK, Winslow MM, Taylor SE, Cashman C, Whittaker CA, et al. Stage-specific sensitivity to p53 restoration during lung cancer progression. Nature 2010;468:572-5. 13. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in nonsmall-cell lung cancer. J Clin Oncol 2007;25:587-95. 14. Liu Y, He W, Long J, Pang F, Xian L, Chen M, et al. Natural selection and functional diversification of the epidermal growth factor receptor EGFR family in vertebrates. Genomics 2013;101:318-25. 15. Uribe P, Gonzalez S. Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: Molecular bases for EGFRtargeted therapy. Pathol Res Pract 2011;207:337-42. 16. Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A, et al. EGFR-targeted therapy for non-small cell lung cancer: Focus on EGFR oncogenic mutation. Int J Med Sci 2013;10:320-30. 17. Li B, Wang C, Zhang Y, Zhao XY, Huang B, Wu PF, et al. Elevated PLGF contributes to small-cell lung cancer brain metastasis. Oncogene 2013;32:2952-62. 18. Salgia R, Hensing T, Campbell N, Salama AK, Maitland M, Hoffman P, et al. Personalized treatment of lung cancer. Semin Oncol 2011;38: 274-83. Cite this article as: Liu Q, Zhou Q. The challenges of lung cancer in China. J Can Res Ther 2013;9:65-6. Source of Support: Nil, Conflict of Interest: No.
Journal of Cancer Research and Therapeutics - Supplement 2 - 2013 - Volume 9
Copyright of Journal of Cancer Research & Therapeutics is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
