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| 1 | Advances in immunotherapy for treatment of lung cancer显示文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1(PD-1) and its ligand(PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab, another anti PD-1 antibody, has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer(NSCLC), supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months. | Jean G.Bustamante Alvarez María González-Cao Niki Karachaliou Mariacarmela Santarpia Santiago Viteri Cristina Teixidó Rafael Rosell | 2015 | Cancer Biology & Medicine2015，12，3： | 22 |
| 2 | Assays for predicting and monitoring responses to lung cancer immunotherapy显示文摘Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1(PD-1) and its ligand(PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer(NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry(IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway. | Cristina Teixidó Niki Karachaliou Maria González-Cao Daniela Morales-Espinosa Rafael Rosell | 2015 | Cancer Biology & Medicine2015，12，2： | 10 |
| 3 | Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints显示文摘Survival rates for metastatic lung cancer, including non-small cell lung cancer(NSCLC) and small cell lung cancer(SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer. | Niki Karachaliou Maria Gonzalez Cao Cristina Teixidó Santiago Viteri Daniela Morales-Espinosa Mariacarmela Santarpia Rafael Rosell | 2015 | Cancer Biology & Medicine2015，12，2： | 10 |
| 4 | Human endogenous retroviruses and cancer显示文摘Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors. | María Gonzalez-Cao Paola Iduma Niki Karachaliou Mariacarmela Santarpia Julià Blanco Rafael Rosell | 2016 | Cancer Biology & Medicine2016，13，4： | 3 |
| 5 | IHC、FISH和RT-PCR检测对EML4-ALK重排的一致性显示文摘棘皮动物微管结合蛋白-间变性淋巴瘤激酶(echinoderm microtubule-associated prote i n-l ike4-anaplastic lymphoma kinase,EML4-ALK)在肺癌中已成为第二个最重要的驱动致癌基因,在4%-6%的肺腺癌中EML4-ALK已经成为第一个可以靶向治疗的融合基因位点。伴随着ALK分离探针荧光原位杂交(fluorescent in situ hybridization,FISH)试剂盒的上市,克唑替尼已经被批准治疗ALK阳性的进展期非小细胞肺癌(non-small cell lung cancer,NSCLC)。然而,一种靶向药物的成功主要取决于一种敏感且特异的筛选实验方法来检测分子药物作用的靶点。以作者的经验看,用RTPCR来检测EML4-ALK,比用FISH和免疫组化(immunohistochemistry,IHC)方法更敏感,结果更可靠。尽管通过FISH检测ALK已经经过大量的临床实验验证,然而该方法在技术层面仍存在许多具有挑战性的问题,而通过IHC和RT-PCR方法检测ALK仍需要临床进一步的探索。 | Cristina Teixidó Niki Karachaliou Vicente Peg Ana Gimenez-Capitan Rafael Rosell 魏建国 许春伟 张博 | 2015 | 临床与病理杂志2015，35，2： | 3 |
| 6 | Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial显示文摘 | Jean-Yves Douillard Rafael Rosell Mario De Lena Francesco Carpagnano Rodryg Ramlau Jose Luis Gonzáles-Larriba Tomasz Grodzki Jose Rodrigues Pereira Alain Le Groumellec Vito Lorusso Claude Clary Antonio J Torres Jabrail Dahabreh Pierre-Jean Souquet Julio A | 2006 | Lancet Oncology2006，，9： | 2 |
| 7 | PD-L1 expression associated with better response to EGFR tyrosine kinase inhibitors显示文摘Cancer evades host immune surveillance by using immune checkpoints,w hich are inhibitor y pathways cr ucial for maintaining self-tolerance1.Tumor cells express multiple inhibitory ligands,and tumor-infiltrating lymphocytes(TIL)express a variety of inhibitory receptors.Inhibitory receptors cytotoxic T-lymphocyte-associated protein 4(CTLA-4)and programmed | Rafael Rosell Ramón Palmero | 2015 | Cancer Biology & Medicine2015，12，2： | 2 |
| 8 | Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial显示文摘 | Rafael Rosell Enric Carcereny Radj Gervais Alain Vergnenegre Bartomeu Massuti Enriqueta Felip Ramon Palmero Ramon Garcia-Gomez Cinta Pallares Jose Miguel Sanchez Rut Porta Manuel Cobo Pilar Garrido Flavia Longo Teresa Moran Amelia Insa Filippo De Marinis | 2012 | Lancet Oncology2012，，3： | 1 |
| 9 | Screening for epi- dermal growth factor receptor mutations in lung cancer 显示文摘 | Rafael Rosell Teresa Moran Cfistina Queralt | 2009 | The new England journal of medicine2009，361，10： | 1 |
| 10 | The cystic fibrosis transmembrane conductance regulator as a biomarkerin non-small cell lung cancer显示文摘 | Jin Li Jie Zhang Xiaohua Jiang Xiaoshun Shi Jianfei Shen Fenglan Feng Jingyi Chen Guihong Liu Ping He Juhong Jiang Lai Tsang Yan Wang Rafael Rosell Long Jiang Jianxing He Hsiao Chan | 2015 | International Journal of Oncology2015，，： | 1 |
| 11 | Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial显示文摘 | Rafael Rosell Enric Carcereny Radj Gervais Alain Vergnenegre Bartomeu Massuti Enriqueta Felip Ramon Palmero Ramon Garcia-Gomez Cinta Pallares Jose Miguel Sanchez Rut Porta Manuel Cobo Pilar Garrido Flavia Longo Teresa Moran Amelia Insa Filippo De Marinis | 2012 | Lancet Oncology2012，，3： | 1 |
| 12 | RAC1b overexpression correlates with poor prognosis in KRAS/BRAF WT metastatic colorectal cancer patients treated with first-line FOLFOX/XELOX chemotherapy显示文摘 | Virginia Alonso-Espinaco Miriam Cuatrecasas Vicente Alonso Pilar Escudero Maribel Marmol Carlos Horndler Javier Ortego Rosa Gallego Jordi Codony-Servat Xabier Garcia-Albeniz Pedro Jares Antoni Castells Juan José Lozano Rafael Rosell Joan Maurel | 2014 | European Journal of Cancer2014，，： | 1 |
| 13 | The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer显示文摘 | Oscar Arrieta Andrés Felipe Cardona Luis Corrales Alma Delia Campos-Parra Roberto Sánchez-Reyes Eduardo Amieva-Rivera July Rodríguez Carlos Vargas Hernán Carranza Jorge Otero Nikki Karachaliou Horacio Astudillo Rafael Rosell | 2014 | Lung Cancer2014，，： | 1 |
| 14 | Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial显示文摘 | Rafael Rosell Enric Carcereny Radj Gervais Alain Vergnenegre Bartomeu Massuti Enriqueta Felip Ramon Palmero Ramon Garcia-Gomez Cinta Pallares Jose Miguel Sanchez Rut Porta Manuel Cobo Pilar Garrido Flavia Longo Teresa Moran Amelia Insa Filippo De Marinis | 2012 | Lancet Oncology2012，，3： | 1 |
| 15 | Nucleotide excision repair pathways involved in cisplatin resistance in non-small-cell lung cancer显示文摘 | Rafael Rosell MD Miquel Taron PhD Agusti Barnadas MD | 2003 | Cancer Control2003，10，4： | 1 |
| 16 | The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients显示文摘 | Carlos Camps Eloisa Jantus-Lewintre Andrea Cabrera Ana Blasco Elena Sanmartín Sandra Gallach Cristina Caballero Nieves del Pozo Rafael Rosell Ricardo Guijarro Rafael Sirera | 2010 | Lung Cancer2010，，3： | 1 |
| 17 | Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial显示文摘 | Rafael Rosell Enric Carcereny Radj Gervais Alain Vergnenegre Bartomeu Massuti Enriqueta Felip Ramon Palmero Ramon Garcia-Gomez Cinta Pallares Jose Miguel Sanchez Rut Porta Manuel Cobo Pilar Garrido Flavia Longo Teresa Moran Amelia Insa Filippo De Marinis | 2012 | Lancet Oncology2012，，3： | 1 |
| 18 | BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer 显示文摘 | Miquel Taron Rafael Rosell | 2004 | Human Mol Genetics2004，13，20： | 1 |
| 19 | Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial显示文摘 | Rafael Rosell José Gómez-Codina Carlos Camps José Javier Sánchez José Maestre José Padilla Antonio Cantó Albert Abad Jordi Roig | 1999 | Lung Cancer1999，，1： | 1 |
| 20 | Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib - treated chemorefractory lung adenocarcinomas显示文摘 | Miguel Taron Yukito Ichinose Rafael Rosell | 2005 | Clin Cancer Res2005，11，16： | 1 |
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