肺腺鳞癌治疗现状与展望
The Current Treatment Status and Outlook for Adenosquamous Carcinoma of the Lung
DOI: 10.12677/jcpm.2025.41130, PDF,   
作者: 肖金原:赣南医科大学第一临床医学院,江西 赣州;袁小亮*:赣南医科大学第一附属医院呼吸与危重症医学科,江西 赣州
关键词: 肺腺鳞癌化学治疗放射治疗靶向治疗免疫治疗Lung Adenosquamous Carcinoma Chemotherapy Radiotherapy Targeted Therapy Immunotherapy
摘要: 肺腺鳞癌(adenosquamous carcinoma of the lung, ASC)是一种罕见但又独特的非小细胞肺癌(NSCLC)特殊类型,具有恶性程度高、侵袭性强、预后差、治疗难度大等特点。随着对ASC发病机制的深入研究,不断有新的治疗策略被开发出来。目前对于ASC患者以铂为基础的双药化疗及针对EGFR、ALK等驱动基因突变的靶向治疗均取得了显著的疗效,此外,免疫治疗也为ASC患者带来了新的治疗选择。虽然现有的多种治疗手段为ASC提供了多样化的干预路径,患者的预后状况却依然不尽人意。因此,本综述将简要概述ASC患者的当前治疗现状,并结合最新临床研究进展,旨在为未来的治疗策略提供新的启示和方向。
Abstract: Adenosquamous Carcinoma of the Lung (ASC), a unique and uncommon variant of Non-Small Cell Lung Cancer (NSCLC), is noted for its high degree of malignancy, aggressive invasiveness, unfavorable prognosis and the complexity of its treatment. With in-depth research into the pathogenesis of ASC, novel therapeutic strategies are continuously being developed. Currently, platinum-based doublet chemotherapy and targeted therapy directed at driver gene mutations such as EGFR and ALK have achieved significant therapeutic effects in patients with ASC. Additionally, immunotherapy has also brought new treatment options for patients with ASC. Despite the availability of various therapeutic approaches that provide diverse intervention pathways for ASC, the prognosis of patients remains unsatisfactory. Therefore, this review will briefly outline the current treatment status of ASC. By incorporating the latest clinical research advancements, this review aims to provide new insights and directions for future therapeutic strategies.
文章引用:肖金原, 袁小亮. 肺腺鳞癌治疗现状与展望[J]. 临床个性化医学, 2025, 4(1): 923-931. https://doi.org/10.12677/jcpm.2025.41130

参考文献

[1] Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., et al. (2024) Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74, 229-263. [Google Scholar] [CrossRef] [PubMed]
[2] Wang, Y. (2024) Comprehensive Analysis of Clinicopathological Profiles in Adenosquamous Carcinoma of the Lung. American Journal of Translational Research, 16, 126-135. [Google Scholar] [CrossRef] [PubMed]
[3] Handa, Y., Ikeda, T., Hanaki, H., Miyata, Y., Mukaida, H. and Okada, M. (2023) Clinicopathologic Study of Stage I Adenosquamous Carcinoma of the Lung. Japanese Journal of Clinical Oncology, 53, 1201-1207. [Google Scholar] [CrossRef] [PubMed]
[4] Zhao, W.J., Wang, X. and Ma, K.W. (2017) Progression of Diagnosis and Treatment for Adenosquamous Lung Carcinoma. Chinese Journal of Oncology, 39, 241-244.
[5] Schneider, B.J., Daly, M.E., Kennedy, E.B., Antonoff, M.B., Broderick, S., Feldman, J., et al. (2018) Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline. Journal of Clinical Oncology, 36, 710-719. [Google Scholar] [CrossRef] [PubMed]
[6] Zhu, S., Ge, T., Xiong, Y., Zhang, J., Zhu, D., Sun, L., et al. (2022) Surgical Options for Resectable Lung Adenosquamous Carcinoma: A Propensity Score-Matched Analysis. Frontiers in Oncology, 12, Article 878419. [Google Scholar] [CrossRef] [PubMed]
[7] Kong, M., Jin, J., Cai, X., Shen, J., Ma, D., Ye, M., et al. (2017) Characteristics of Lymph Node Metastasis in Resected Adenosquamous Lung Cancer. Medicine, 96, e8870. [Google Scholar] [CrossRef] [PubMed]
[8] Liu, S., Wan, S., Feng, J., Pang, Y., Wang, H., Zeng, H., et al. (2024) Meta-Analysis of the Efficacy of Postoperative Adjuvant Chemotherapy for Stage IB Non-Small Cell Lung Cancer. Medicine, 103, e36839. [Google Scholar] [CrossRef] [PubMed]
[9] Kwon, J. and Kim, B.H. (2024) Risk of Clinically Significant Cardiovascular Disease Associated with Postoperative Radiotherapy in Non-Small Cell Lung Cancer Patients Receiving Surgical Resection Followed by Adjuvant Chemotherapy: A Korean Nationwide Cohort Study. Radiotherapy and Oncology, 195, Article 110241. [Google Scholar] [CrossRef] [PubMed]
[10] Ettinger, D.S., Wood, D.E., Aisner, D.L., et al. (2023) NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2. Journal of the National Comprehensive Cancer Network, 21, 340-350.
[11] 林小峰, 陈龙. 晚期非小细胞肺癌化疗现状及进展[J]. 广西医科大学学报, 2019, 36(5): 850-855.
[12] 吴仕文, 郑新龙, 徐贻佺, 徐海鹏, 张龙凤, 刘涛, 李冰, 等. 晚期肺腺鳞癌患者不同一线化疗方案疗效观察[J]. 中华实用诊断与治疗杂志, 2024, 38(1): 86-91.
[13] 王莉, 梁嵘, 刘志辉, 林燕, 等. 晚期肺腺鳞癌不同化疗方案疗效分析[J]. 西部医学, 2016, 28(6): 840-844.
[14] Feng, Z., Pang, Q., Ji, K., et al. (2012) Analysis of the Prognostic Factors in Resection of 181 Patients with Adenosquamous Lung Carcinoma. Chinese Journal of Clinical Oncology, 39, 1656-1659.
[15] Csiki, E., Simon, M., Papp, J., Barabás, M., Mikáczó, J., Gál, K., et al. (2024) Stereotactic Body Radiotherapy in Lung Cancer: A Contemporary Review. Pathology and Oncology Research, 30, Article 1611709. [Google Scholar] [CrossRef] [PubMed]
[16] Khalifa, J., Lerouge, D., et al. (2022) Radiotherapy for Primary Lung Cancer. Cancer Radiotherapie: Journal de la Societe francaise de radiotherapie oncologique, 26, 231-243.
[17] Ni, J., Zheng, Z., Li, J., Li, Y., Fan, M. and Liu, L. (2020) Risk Factors of Postoperative Recurrence and Potential Candidate of Adjuvant Radiotherapy in Lung Adenosquamous Carcinoma. Journal of Thoracic Disease, 12, 5593-5602. [Google Scholar] [CrossRef] [PubMed]
[18] Miao, D., Zhao, J., Han, Y., Zhou, J., Li, X., Zhang, T., et al. (2023) Management of Locally Advanced Non-Small Cell Lung Cancer: State of the Art and Future Directions. Cancer Communications, 44, 23-46. [Google Scholar] [CrossRef] [PubMed]
[19] Xing, H., Wu, C., Zhang, D. and Zhang, X. (2024) Distant Organ Metastasis Patterns and Prognosis of Lung Adenosquamous Carcinoma: A SEER Database Analysis. Interdisciplinary CardioVascular and Thoracic Surgery, 38, ivae007. [Google Scholar] [CrossRef] [PubMed]
[20] Henschke, C.I., Yip, R., Sun, Q., et al. (2024) Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery. Journal of Thoracic Oncology, 19, 476-490.
[21] Ming, X., Mao, J., Ma, N., Chen, J., Wang, W., Sheng, Y., et al. (2024) Intensity-Modulated Proton and Carbon-Ion Radiotherapy Using a Fixed-Beam System for Locally Advanced Lung Cancer: Dosimetric Comparison with X-Ray Radiotherapy and Normal Tissue Complication Probability (NTCP) Evaluation. Physics in Medicine & Biology, 69, Article 015025. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, H., Liu, J., Zhu, S., Miao, K., Li, Z., Qi, X., et al. (2022) Comprehensive Analyses of Genomic Features and Mutational Signatures in Adenosquamous Carcinoma of the Lung. Frontiers in Oncology, 12, Article 945843. [Google Scholar] [CrossRef] [PubMed]
[23] Zhao, R., Xu, Y., Chen, Y., Zhang, J., Teng, F., Liao, S., et al. (2023) Clonal Dynamics and Stereo-Seq Resolve Origin and Phenotypic Plasticity of Adenosquamous Carcinoma. npj Precision Oncology, 7, Article No. 80. [Google Scholar] [CrossRef] [PubMed]
[24] Rubio, K., Romero-Olmedo, A.J., Sarvari, P., Swaminathan, G., Ranvir, V.P., Rogel-Ayala, D.G., et al. (2023) Non-canonical Integrin Signaling Activates EGFR and RAS-MAPK-ERK Signaling in Small Cell Lung Cancer. Theranostics, 13, 2384-2407. [Google Scholar] [CrossRef] [PubMed]
[25] Yu, J., Zhang, L., Peng, J., Ward, R., Hao, P., Wang, J., et al. (2022) Dictamnine, a Novel C-Met Inhibitor, Suppresses the Proliferation of Lung Cancer Cells by Downregulating the PI3K/AKT/mTOR and MAPK Signaling Pathways. Biochemical Pharmacology, 195, Article 114864. [Google Scholar] [CrossRef] [PubMed]
[26] Shi, X., Wu, H., Lu, J., Duan, H., Liu, X. and Liang, Z. (2016) Screening for Major Driver Oncogene Alterations in Adenosquamous Lung Carcinoma Using PCR Coupled with Next-Generation and Sanger Sequencing Methods. Scientific Reports, 6, Article No. 22297. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, M., Xiao, K. and Yang, L. (2023) EGFR Inhibitor Erlotinib Plus Monoclonal Antibody versus Erlotinib Alone for First-Line Treatment of Advanced Non-Small Cell Lung Carcinoma: A Systematic Review and Meta-Analysis. International Immunopharmacology, 119, Article 110001. [Google Scholar] [CrossRef] [PubMed]
[28] Lin, G., Li, C., Li, P.S., Fang, W.Z., Xu, H.P., Gong, Y.H., et al. (2020) Genomic Origin and EGFR-TKI Treatments of Pulmonary Adenosquamous Carcinoma. Annals of Oncology, 31, 517-524. [Google Scholar] [CrossRef] [PubMed]
[29] Cai, Z., Huang, J., Dai, W., Li, X., Hong, W. and Hong, Y. (2024) Complete Pathologic Response to Neoadjuvant Icotinib in Stage IIIA EGFR-Mutant Lung Adenosquamous Carcinoma: A Case Report. Medicine, 103, e36214. [Google Scholar] [CrossRef] [PubMed]
[30] Zhang, N., Chen, S., Guo, L. and Chen, X. (2021) A Case Report of Right Upper Lung Adenosquamous Carcinoma Resection Following Neoadjuvant Targeted Therapy. Annals of Palliative Medicine, 10, 4987-4993. [Google Scholar] [CrossRef] [PubMed]
[31] Planchard, D. (2020) Adjuvant Osimertinib in EGFR-Mutated Non-Small-Cell Lung Cancer. New England Journal of Medicine, 383, 1780-1782. [Google Scholar] [CrossRef] [PubMed]
[32] Huo, R., Li, J., Li, X., Shi, J., Wang, K., Jiao, J., et al. (2020) Significant Benefits of Osimertinib against Adenosquamous Carcinoma Harboring Germline T790M Mutation. The Oncologist, 25, 826-832. [Google Scholar] [CrossRef] [PubMed]
[33] Yamaguchi, F., Kato, E., Wakabayashi, A. and Shikama, Y. (2019) Effect of Osimertinib Treatment on Lung Adenocarcinoma with Squamous Cell Transformation Harboring the T790M Mutation: A Case Report and Literature Review. Molecular and Clinical Oncology, 11, 127-131. [Google Scholar] [CrossRef] [PubMed]
[34] Kim, S., Kim, K.E., Kim, Y. and Chung, C. (2023) A Patient with a Lung Adenosquamous Carcinoma Harboring a de Novo T790m Mutation and Huge Nonbacterial Vegetative Growths Successfully Treated with Osimertinib: A Case Report. Thoracic Cancer, 14, 1530-1533. [Google Scholar] [CrossRef] [PubMed]
[35] Harris, E. and Thawani, R. (2024) Current Perspectives of KRAS in Non-Small Cell Lung Cancer. Current Problems in Cancer, 51, Article 101106. [Google Scholar] [CrossRef] [PubMed]
[36] Jänne, P.A., Riely, G.J., Gadgeel, S.M., Heist, R.S., Ou, S.I., Pacheco, J.M., et al. (2022) Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS g12c Mutation. New England Journal of Medicine, 387, 120-131. [Google Scholar] [CrossRef] [PubMed]
[37] Tsamis, I., Gomatou, G., Chachali, S.P., Trontzas, I.P., Patriarcheas, V., Panagiotou, E., et al. (2022) BRAF/MEK Inhibition in NSCLC: Mechanisms of Resistance and How to Overcome It. Clinical and Translational Oncology, 25, 10-20. [Google Scholar] [CrossRef] [PubMed]
[38] Yan, N., Guo, S., Zhang, H., Zhang, Z., Shen, S. and Li, X. (2022) Braf-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. Frontiers in Oncology, 12, Article 863043. [Google Scholar] [CrossRef] [PubMed]
[39] Hossain, M.A. (2024) Targeting the RAS Upstream and Downstream Signaling Pathway for Cancer Treatment. European Journal of Pharmacology, 15, Article 176727.
[40] Liu, X., Mei, W., Zhang, P. and Zeng, C. (2024) PIK3CA Mutation as an Acquired Resistance Driver to EGFR-TKIS in Non-Small Cell Lung Cancer: Clinical Challenges and Opportunities. Pharmacological Research, 202, Article 107123. [Google Scholar] [CrossRef] [PubMed]
[41] Yu, Z., Wang, M., Zhou, W., Mao, M., Chen, Y., Li, N., et al. (2022) ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Biology, Diagnostics, Therapeutics and Resistance. Journal of Drug Targeting, 30, 845-857. [Google Scholar] [CrossRef] [PubMed]
[42] Stanzione, B., Del Conte, A., Bertoli, E., De Carlo, E., Revelant, A., Spina, M., et al. (2023) Therapeutical Options in ROS1—Rearranged Advanced Non-Small Cell Lung Cancer. International Journal of Molecular Sciences, 24, Article 11495. [Google Scholar] [CrossRef] [PubMed]
[43] Drilon, A., Camidge, D.R., Lin, J.J., Kim, S., Solomon, B.J., Dziadziuszko, R., et al. (2024) Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. New England Journal of Medicine, 390, 118-131. [Google Scholar] [CrossRef] [PubMed]
[44] Cheng, Y., Yang, J., Wang, D. and Yan, D. (2022) ROS1 Fusion Lung Adenosquamous Carcinoma Patient with Short-Term Clinical Benefit after Crizotinib Treatment: A Case Report. Annals of Translational Medicine, 10, 157-157. [Google Scholar] [CrossRef] [PubMed]
[45] Peng, L., Zhu, L., Sun, Y., Stebbing, J., Selvaggi, G., Zhang, Y., et al. (2022) Targeting ALK Rearrangements in NSCLC: Current State of the Art. Frontiers in Oncology, 12, Article 863461. [Google Scholar] [CrossRef] [PubMed]
[46] Ding, L., Yuan, X., Wang, Y., Yang, M., Wu, P., Chen, H., et al. (2024) Ensartinib in the Treatment of Anaplastic Lymphoma Kinase-Positive Locally Advanced or Metastatic Patients with Lung Squamous or Adenosquamous Carcinoma: A Real-World, Retrospective Study. Asia-Pacific Journal of Clinical Oncology, 20, 700-706. [Google Scholar] [CrossRef] [PubMed]
[47] Mai, S., Wang, Y., Wang, X., Yang, W., Gao, H., Xu, Z., et al. (2022) Neoadjuvant Ceritinib Treatment in ALK-Rearranged Locally Advanced Adenosquamous Carcinoma: A Case Report. Thoracic Cancer, 13, 2275-2278. [Google Scholar] [CrossRef] [PubMed]
[48] Qin, Y., Li, F., Tan, Y., Duan, Q. and Zhang, Q. (2022) Case Report: Dramatic Response to Alectinib in a Lung Adenosquamous Carcinoma Patient Harbouring a Novel CPE-ALK Fusion. Frontiers in Oncology, 12, Article 998545. [Google Scholar] [CrossRef] [PubMed]
[49] Mountzios, G., Remon, J., Hendriks, L.E.L., García-Campelo, R., Rolfo, C., Van Schil, P., et al. (2023) Immune-Checkpoint Inhibition for Resectable Non-Small-Cell Lung Cancer—Opportunities and Challenges. Nature Reviews Clinical Oncology, 20, 664-677. [Google Scholar] [CrossRef] [PubMed]
[50] Li, Y., Liang, X., Li, H. and Chen, X. (2023) Efficacy and Safety of Immune Checkpoint Inhibitors for Advanced Non-Small Cell Lung Cancer with or without PD-L1 Selection: A Systematic Review and Network Meta-Analysis. Chinese Medical Journal, 136, 2156-2165. [Google Scholar] [CrossRef] [PubMed]
[51] Liu, Y., Dong, Z., Jiang, T., Hou, L., Wu, F., Gao, G., et al. (2018) Heterogeneity of PD-L1 Expression among the Different Histological Components and Metastatic Lymph Nodes in Patients with Resected Lung Adenosquamous Carcinoma. Clinical Lung Cancer, 19, e421-e430. [Google Scholar] [CrossRef] [PubMed]
[52] Wei, J., Xiang, J., Hao, Y., Si, J., Gu, X., Xu, M., et al. (2023) Clinical Outcomes of Immune Checkpoint Inhibitor Therapy for Advanced Lung Adenosquamous Carcinoma. Journal of Thoracic Disease, 15, 260-269. [Google Scholar] [CrossRef] [PubMed]
[53] Li, C., Zheng, X., Li, P., et al. (2022) Heterogeneity of Tumor Immune Microenvironment and Real-World Analysis of Immunotherapy Efficacy in Lung Adenosquamous Carcinoma. Frontiers in Immunology, 13, Article 944812.