陆舜教授： 有的放矢，做肺癌研究领域的“领潮儿”

引言：近年来肺癌的高发病率和死亡率，让不少人都谈“癌”色变。中国在肺癌的治疗和临床研究进展如何？面临什么样挑战？作为在肺癌领域颇有建树的上海胸科医院又经历哪些发展和变化？带着这些疑问，我们有幸采访了在肺癌领域造诣颇深的陆舜教授。

数字见证发展，人才引领未来

谈到胸科医院肿瘤科的发展史，陆教授满脸的自豪。肿瘤科的成立得益于两位极具话语权的前辈——廖美琳、周允中教授。这两位老师在2000年意识到肿瘤治疗不是单一学科能够解决的，这一前瞻性的认识推动了肿瘤科的成立。2006年，肿瘤科成立，使得内外科真正整合在了一起，完成了多学科团队的建设。作为胸科医院临床大科室中最年轻的科室，肿瘤科建科十多年来，发展日新月异。从建科时只有500例的手术量到去年2500例的突破；内科治疗的入院人次从2000到9000的超越；从获得省市级科研项目再到拿下国家重大专项研究的飞跃；科室团队发表的SCI文章从无到有，再到每年40多分的姣好成绩；这些数字见证了肿瘤科一个又一个的里程碑，其整体的规模、人员的素质都在突飞猛进。通过十多年的建设，团队的凝聚力、专业技术使得胸科医院肿瘤科走在中国肺癌领域的前端，与其他同道共同推动着中国肺癌工作的进展。

作为内外科兼具的肿瘤科的主任，陆教授对于内科和外科的见解很深刻。陆教授认为外科的发展重点在于“一大一小“：“大”到器官移植（肺移植）、人工器官的替换，“小”到微创手术，而肿瘤科在这两方面都极具人才优势。完成瑞士苏黎世大学医学博士和博士后培训的谭强教授，在组织工程方面造诣颇深，成功完成了人工气管的手术，再生医学也是其研究的重点方向。进行中国第一例机器人达芬奇肺癌手术的罗清泉教授，微创手术量一直位居全国前列，罗教授紧握外科发展的方向，走的又快又稳。在内科方面，陆教授强调转化医学在肿瘤内科治疗的应用，要不断推动临床免疫学靶标的建立，推动精准医疗的落实。不断探索以基因医学、临床肿瘤免疫学为基础的个体化医疗，争取最大把握的治疗患者。

谈到肿瘤科在外科方面的人才优势，陆教授便与我们分享了他对年轻医生培养的看法。陆教授语重心长的说：“年轻医生首先要有‘医德’。要有一颗医者的仁心，愿意奉献，愿意全身心投入医学事业；其次，要有‘仁术’。这就要求管理者、导师为年轻人提供良好的学习环境，制定系统的培养计划，指引明确的研究方向。目标确定了，年轻人再不断学习、进步，这样才能有所得，才能培养出引领未来发展的优秀的人才。”

从“赶潮儿”到“弄潮儿”的跨越

肺癌治疗在这二十多年经历着巨大的更迭和创新。从1995年到2005年，研究学者不断发现不具个体化特征的化疗手段发展进程极为有限，并不是未来肿瘤治疗的方向。从2005年到2015年，具有特异性的靶向治疗成为肺癌治疗的主力军。从2015年至今，免疫治疗进入人们的视野，成为最新最具潜力的研究热点。作为肿瘤科主任，陆教授早在美国启动TCGA计划之时，就敏锐的感觉到基因组学开始进入临床，于是开始重视起基因组学的临床和转化研究，带领着科室开展了肺癌的个体化治疗研究。陆教授指出，化疗的“试错”时代已经过去，有关biomark的研究才是未来肺癌治疗的方向。

肿瘤科紧跟国际肺癌研究发展进程，做了大量与国际接轨的研究。陆教授和其团队在《P Natl Acad Sci USA》上发表了有关在体液样本中快速鉴定肿瘤细胞的新方法的文章。在研究中他们发现，相比于Veridex公司（Veridex公司是强生的一个子公司）的Cell search CTCs检测技术，这一新技术在循环肿瘤细胞检测中颇具优势。肿瘤科还参与了全球性的LUX-Lung 8研究，探讨了晚期肺鳞癌的标准二线治疗药物。这一研究作为美国的注册研究，胸科医院提供的患者数据接受了美国FDA的检查；也作为在中国取得适应症的研究，颇具研究价值。除此之外，在免疫辅助治疗方面，肿瘤科也参与了国际的多中心临床试验研究。依托上海胸科医院在肺癌领域探索的积淀，肿瘤科作为肺癌治疗研究的中心，科研是其重心，也承担了很多药物注册的研究。改变中国肺癌的标准治疗，改变指南，引领未来肺癌的发展是肿瘤科一直奋斗的目标。走向国际化，是中国临床研究的必然。

如果将中国肺癌的研究进程分成三个阶段，陆教授认为，从1999年到2009年，我们是肺癌领域的“赶潮儿”。在1999年前中国没有国家药监局，没有GCP原则，临床试验不符合国际规范。到了2009年，吴一龙教授和莫树锦教授将IPASS研究（吉非替尼治疗非小细胞肺癌的研究）结果发表在《N Engl J Med》上，拉开了肺癌的分子靶向治疗的新篇章，改变了全球肺癌的标准治疗，也让中国肺癌的研究开始进入快车道。在这个阶段中，我们在跟着先进的国家学习，还没有独立设计实验的思路，还没有话语权。放眼2009年到2019年这十年，我们是肺癌领域的“弄潮儿”。中国学者参与了很多国际重要研究方案的讨论，有的甚至开始担任主要研究者。2016年，吴一龙教授和莫树锦教授的关于奥希替尼（AZD9291）治疗吉非替尼耐药后T790突变的肺癌的研究AURA3再次登陆《N Engl J Med》，这表明中国肺癌治疗的探索和研究又向前迈进了一大步。

而2019年以后，陆教授坚定的说，我们将会成为肺癌领域的“领潮儿”。回首一路的探索，中国肺癌的临床实验和研究走了一条非常正确的道路。 

认清差距，争做肺癌研究领域的“领潮儿”

多次赴国外进修的经验也让陆教授看到了国内肿瘤科和国外的差距：实验同临床的结合不足，诊断理念有待更新。国内一些肿瘤科室对于未来肿瘤领域的发展方向把控不准，科室的实验条件不完善，没有将实验深入到临床，创新条件还不够成熟。在诊断理念方面，国内内科肿瘤的治疗通常基于一次活检诊断。但最近《N Engl J Med》刊登了几篇有关肿瘤进化的重磅研究，这一概念的提出和深入探索，就要求我们在肿瘤治疗的过程中动态的观察其是否变化，怎样变化，该怎样治疗。而这一点，国内还没有形成系统清晰的理念。因此，在准确把握肺癌发展方向的基础上，我们要努力实现精准医疗。精准医疗重点在精准，落实在医疗。我们要以临床为中心，以临床需求为导向，致力于作出能够改变临床实践的研究，真正践行“from bench to bed，from bed to bench”这一理念。只要我们有足够好的理念，未来我们不仅会成为肺癌研究领域的大国，更会成为此领域的强国，成为“领潮儿”更是指日可待。

当问及对于 Shanghai Chest 这一期刊的期待，陆教授希望这本期刊能够借鉴和吸取国外优秀期刊的优点和长处，找到适合其发展的模式，脚踏实地，争取发表出高质量的文章，逐渐做出自己的特色，在胸科领域的期刊中能够有一席之地。

从“赶潮儿”到“弄潮儿”的超越，再到“领潮儿”的设想和信心，这三个词的变化见证了中国在肺癌领域治疗和临床研究的深刻变革，也目睹了陆教授等优秀的肿瘤科医生多年来攻坚克难，砥砺前行的执着。不忘初心，直面挑战，上海胸科医院肿瘤科定能够继续在国际上大放光彩，中国肺癌的诊治和研究定当日臻完善。

摘自：AME科研实践   采写编辑：刘黎畅 周丽桃  AME Publishing Company

临床试验类

Lancet Oncol First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised,  open-label, phase 3 trial Shun Lu（2021）

Lung Cancer Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078) Shun Lu (2020)

Clin Cancer Res Clonal architecture of EGFR mutation predicts the efficacy of EGFR-Tyrosine Kinase Inhitors in advanced NSCLC: a prospective multicenter study (NCT03059641) Shun Lu (2020)

Lung Cancer A phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer-the FALUCA study Shun Lu (2020)Lancet Respir Med  Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial  Shun Lu (2020)

Transl Lung Cancer Res  Biosimilar candidate IBI305 plus paclitaxel/carboplatin for the treatment of non-squamous non-small cell lung cancer  Shun Lu (2020)

Front Oncol  A randomized phase III study of Abemaciclib versus Erlotinib in patients with stage IV non-small cell lung cancer with a detectable KRAS mutation who failed prior Platinum-based therapy: JUNIPER  Shun Lu (2020)

J Thorac Oncol Salvage therapy for locoregional recurrence after stereotactic ablative radiotherapy for early-stage non-small cell lung cancer Shun Lu (2020)

J Thorac Oncol Safety, Efficacy and pharmacokinetics of almonertinib (HS-10296) in pretreated patients with EGFR-mutated advanced NSCLC: a multicenter, open-label, phase I trial Shun Lu (2020)

Lancet Respir Med Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial  Shun Lu (2020)

N Engl J Med Osimertinib in resected EGFR-mutated non-small-cell lung cancer   Shun Lu (2020)

J Thorac Oncol Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC: CheckMate 078 randomized phase III clinical trial  Shun Lu (2019)

Lung Cancer Erlotinib versus gemcitabine/cisplatin in Chinese patients with EGFR mutation-positive advanced non-small-cell lung cancer: Crossover extension and post-hoc analysis of the ENSURE study Shun Lu (2019)

Lung Cancer  First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders in the LUX-Lung 3, 6, and 7 trials Shun Lu (2019)

J Thorac Oncol The unique spatial-temporal treatment failure patterns of adjuvant Gefitinib Therapy: A Post Hoc  analysis of the ADJUVANT trial (CTONG 1104)  Mei-lin Liao (2018)

Onco Targets Ther Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring EGFR mutations: subgroup analysis of the LUX-Lung 6 trial  Shun Lu (2018)

Lung Cancer  Clinical utility of a blood-based EGFR mutation test in patients receiving first-line erlotinib therapy in the ENSURE, FASTACT-2, and ASPIRATION studies  Shun Lu (2018)

J Clin Oncol  Randomized, double-blind, placebo-controlled, multicenter phase II study of fruquintinib after two prior chemotherapy regimens in Chinese patients with advanced nonsquamous non-small-cell lung cancer  Shun Lu (2018)

J Thorac Oncol  Nedaplatin plus docetaxel versus cisplatin plus docetaxel as first-line chemotherapy for advanced squamous cell carcinoma of the lung-A multicenter, open-label, randomized, phase III trial Shun Lu (2018)

J Thorac Oncol Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-Positive advanced non-small cell lung cancer Shun Lu (2018)

JAMA Oncol  Association of ERBB mutations with clinical outcomes of afatinib-or erlotinib-treated patients with lung squamous cell carcinoma secondary analysis of the LUX-Lung 8 randomized clinical trial  Shun Lu (2018)

J Clin Oncol  Phase II study of crizotinib in East Asian patients with ROS1-positive advanced non-small-cell lung cancer  Shun Lu (2018)

Lung Cancer Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study Shun Lu (2017)

Ann Oncol Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer)  Shun Lu (2017)

J Thorac Oncol  Results of PROFILE 1029, a phase III comparison of first-line Crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer  Shun Lu (2017)

Ann Oncol  Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials  Shun Lu (2016)

Ann  Oncol  Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial  Shun Lu (2016)

Lancet Oncol Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung7): a phase 2B, open-label, randomized controlled trial  Shun Lu (2016)

Br J Cancer  EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6  Shun Lu (2016)

Lancet Respir Med  Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicenter, phase 3, open-label, parallel, randomised controlled trial  Shun Lu (2016)

Asia-Pacific J Clin Oncol  An East Asian subgroup analysis of PROCLAIM, a phase III trial of pemetrexed and cisplatin or etoposide and cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small cell lung cancer  Shun Lu (2016)

Lancet Oncol  Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial  Mei-lin Liao (2016)

J Thorac Oncol A multicenter, open-label, randomized phase II controlled study of rh-Endostatin (Endostar) in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer Shun Lu (2015)

Lancet Oncol  Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial  Shun Lu (2015)

Lancet Oncol Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials  Shun Lu (2015)

Ann Oncol First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study  Shun Lu (2015)

Ann Oncol Final overall survival results from a randomised, Phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802) Shun Lu (2015)

Ann Oncol  Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial  Shun Lu (2015)

J Thorac Oncol  Final overall survival results from a phase III, randomized,

placebo-controlled, parallel-group study of gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804)  Shun Lu (2015)

J Thorac Oncol  Symptom and quality of life improvement in LUX-Lung 6: An open-label phase III study of afatinib versus cisplatin/gemcitabine in Asian patients with EGFR mutation-positive advanced non-small cell lung cancer  Shun Lu (2015)

Jpn J Clin Oncol  Efficacy of erlotinib in previously treated patients with advanced non-small cell lung cancer: analysis of the Chinese subpopulation in the TRUST study Mei-lin Liao (2015)

Eur J Cancer Analysis of patient-reported outcomes from the LUME-Lung 1 trial: a randomised, double-blind, placebo-controlled, Phase III study of second-line nintedanib in patients with advanced non-small cell lung cancer  Mei-lin Liao (2015)

Clin Cancer Res  Detection and dynamic changes of EGFR mutations from circulating tumor DNA as a predictor of survival outcomes in NSCLC patients treated with first-line intercalated Erlotinib and chemotherapy Mei-lin Liao (2015)

Lancet Oncol Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial  Mei-Lin Liao (2014)

J Clin Oncol BEYOND: A randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer  Shun Lu (2014)

Lung Cancer Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer  Shun Lu (2014)

Lancet Oncol  Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial Shun Lu (2014)

Lancet Oncol  Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial  Mei-Lin Liao (2013)

Ann Oncol  Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and a symptomatic brain metastases: a phase II study (CTONG-0803)  Shun Lu (2013)

Asia-Pacific J Clin Oncol  Phase III, randomized, open-label, first-line study in Asia of gefitinib versuscar boplatin/paclitaxel in clinically selected patients with advanced non-small-cell  lung cancer: evaluation of patients recruited from China  Mei-Lin Liao (2012)

J Clin Oncol Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer Mei-Lin Liao (2012)

Lancet Oncol Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial  Shun Lu (2012)

Lancet Oncol  Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study  Shun Lu (2011)

J Thorac Oncol Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS) Mei-lin Liao (2011)

J Clin Oncol Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial  Mei-lin Liao (2010)

J Clin Oncol  Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer  Mei-lin Liao (2009)

Lancet  Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial   Mei-lin Liao (2008)

Chin Med J Gemcitabine and cisplatin treatment over a 3-week versus a 4-week dosing schedule: a randomized trial conducted in Chinese patients with nonsmall cell lung cancer  Mei-lin Liao (2008)

转化研究类

Transl Lung Cancer Res The effect of PD-L1 categories-directed pembrolizumab plus chemotherapy for newly diagnosed metastatic non-small-cell lung cancer: a cost-effectiveness analysis  Shun Lu (2021)

Transl Lung Cancer Res  Circulating tumor DNA clearance predicts prognosis across treatment regimen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort Shun Lu (2020)

Oncogenesis Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer Shun Lu (2019)

EBioMedicine Value of folate receptor-positive circulating tumor cells in the clinical management of indeterminate lung nodules: A non-invasive biomarker for predicting malignancy and tumor invasiveness Shun Lu (2019)

J Thorac Oncol The diversity of gut microbiome is associated with favorable responses to anti-PD-1 immunotherapy in Chinese non-small cell lung cancer patients  Shun Lu (2019)

Nat Commun Liquid biopsy-based single-cell metabolic phenotyping of lung cancer patients for informative diagnostics Shun Lu (2019)

J Thorac Oncol EGFR and ERBB2 germline mutations in Chinese lung cancer patients and their roles in genetic susceptibility to cancer Shun Lu (2019)

J Thorac Oncol Durable clinical response of lung adenocarcinoma harboring EGFR 19del/T790M/in trans-C797S to combination therapy of first-and third-generation EGFR TKIs Shun Lu (2019)

Oncogene FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial–mesenchymal transition, and metastasis in FGFR1-amplified lung cancer Shun Lu (2018)

J Thorac Oncol  Efficacy of crizotinib among different types of ROS1 fusion partners in patients with ROS1-rearranged non-small-cell lung cancer Shun Lu (2018)

Cancer Commun  Xenograft tumors derived from malignant pleural effusion of the patients with non‑small‑cell lung cancer as models to explore drug resistance  Shun Lu (2018)

Cancer Lett The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer  Shun Lu (2018)

J Exp Clin Cancer Res  SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4 Shun Lu (2018)

J Exp Clin Cancer Res  FGF2/FGFR1 regulates autophagy in FGFR1-amplified non-small cell lung cancer cells Shun Lu (2017)

P Natl Acad Sci USA  High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients Shun Lu (2017)

Clin Cancer Res  Genome-wide DNA methylation analysis reveals GABBR2 as a novel epigenetic target for EGFR 19 deletion lung adenocarcinoma with induction erlotinib treatment  Shun Lu (2017)

J Cell Mol Med 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway Shun Lu (2015)

Clin Cancer Res TERT polymorphism rs2736100-C is associated with EGFR mutation-positive non-small cell lung cancer Shun Lu (2015)Br J Pharmacol  hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung caner Shun Lu (2014)

Chest Prognostic significance of the extent of lymph node involvement in stage II-N1 non-small cell lung cancer  Shun Lu (2012)

J Thorac Oncol A study of ethnic differences in TGFβ1 gene polymorphisms and effects on the risk of radiation pneumonitis in non-small-cell lung cancer Shun Lu (2012)

J Thorac Oncol  Association of the CHRNA3 locus with lung cancer risk and prognosis in Chinese Han population  Shun Lu (2010)

J Thorac Oncol Analysis of the T descriptors and other prognosis factorsin pathologic stage I non-small cell lung cancer in China  Shun Lu (2010)

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