From icing to slicing the cake: the new hope of precision medicine for lung cancer
Editorial

从“冰冻蛋糕”到“切割蛋糕”：肺癌精准治疗的新希望

“Έτσι, δεν γνωρίζω”是著名的苏格拉底格言，译为“我知道我的无知”。这不仅仅是一种谦逊的说法，更是五世纪希腊哲学家一种开放而高明的学习方法。对于肺癌诊断和治疗方面取得的进展，用这句话描述恰到好处，特别是在过去的10年中。过去的30年里，我们对肺癌的研究从早先的基于肿瘤器官学向基于形态学的过渡，进而向前迈进到了一种以遗传或基因组为基础的医学（即精准医学）。在九十年代，肺癌的诊断足以为每位患者提供系统化治疗。二十世纪的前二十年，我们根据组织学亚型提供了更多元、更积极的治疗。在这两个时代，由于对肿瘤致病因素的认知还很匮乏，我们倾向于基于肿瘤的发生、发展机制来结合和升级治疗方案。在21世纪的前十年里，随着有效靶向治疗被发现，人们逐渐寻找到了驱动肿瘤发生、发展的致病基因，这些为基于新的转化方法治疗肺癌提供了新的视野[1]。肺癌治疗的进一步发展取决于基线时肿瘤标志的基因组特征和对靶向治疗的原发性和继发性耐药机制的分子动态监测[2]。精准医学问世大约十年后的现在，大约每4位非小细胞肺癌（NSCLC）患者中就有1位可以接受靶向药物治疗，这些靶向药物针对肺癌发生、发展过程中的8种致癌基因（EGFR、ALK、ROS1、BRAF、KRASG12C、MET、NTRK、RET）[3−5]。与化疗相比，靶向药物活性更高、毒性通常更小，也更方便。此外，其中一些基因可能是不同肿瘤亚型（即BRAF、NTRK、RET）的致病因素和可被调控的，并导致基于新试验设计（如“篮子”试验）的抗癌药物被不可知论批准[6]。除了基因组改变外，程序性细胞死亡配体1 (PD−L1)和/或肿瘤突变负荷(TMB)的高细胞表达可用于NSCLC患者进行免疫治疗[7,8]。与此同时，我们必须面对新的复杂诊断和治疗挑战。尽管有这些新的治疗方法并使得治疗窗口过渡到疾病的早期阶段，但对于大多数患者来说，肺癌仍然无法被治愈[9]。我们仍然无法检测或靶向肿瘤分子致病因素，也无法处理针对靶向药物和免疫疗法的原发性或继发性耐药现象[10,11]。因此协调各种诊断分析方法并使它们广泛用于分子层面的分析和检测是非常有必要的[12]。以上就是现在和未来关于胸部肿瘤精准医学专题系列的主题。

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Precision Cancer Medicine for the series “Non-Small Cell Lung Cancer”. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://pcm.amegroups.com/article/view/10.21037/pcm-21-39/coif). The series “Non-Small Cell Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. AA and GLB served as the unpaid Guest Editors of the series. AA serves as an unpaid Associate Editor-in-Chief of Precision Cancer Medicine from December 2019 to November 2021. GLB reports consulting fee from AstraZeneca, Roche and Astellas, support for attending meetings and/or travel from AstraZeneca and Ipsen. AA reports personal fees from AstraZeneca, Pfizer, Takeda, Roche, Takeda, MSB, and BMS, as well as grants and personal fees from Boehringer-Ingelheim, outside the submitted work. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

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  3. Addeo A, Banna GL, Friedlaender A. KRAS G12C Mutations in NSCLC: From Target to Resistance. Cancers (Basel) 2021;13:2541. [Crossref] [PubMed]
  4. Friedlaender A, Drilon A, Banna GL, et al. The METeoric rise of MET in lung cancer. Cancer 2020;126:4826-37. [Crossref] [PubMed]
  5. Frisone D, Friedlaender A, Malapelle U, et al. A BRAF new world. Crit Rev Oncol Hematol 2020;152:103008. [Crossref] [PubMed]
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  7. Banna GL, Cortellini A, Cortinovis DL, et al. The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer. ESMO Open 2021;6:100078. Erratum in: ESMO Open 2021;6:100137. [Crossref] [PubMed]
  8. Addeo A, Friedlaender A, Banna GL, et al. TMB or not TMB as a biomarker: That is the question. Crit Rev Oncol Hematol 2021;163:103374. [Crossref] [PubMed]
  9. Addeo A, Banna GL, Friedlaender A. ADAURA: Mature Enough for Publication, Not for Prime Time. Oncologist 2021;26:266-8. [Crossref] [PubMed]
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  12. Torres GF, Bonilla CE, Buitrago G, et al. How clinically useful is comprehensive genomic profiling for patients with non-small cell lung cancer? A systematic review. Crit Rev Oncol Hematol 2021;166:103459. [Crossref] [PubMed]
Giuseppe L. Banna
Alfredo Addeo

Giuseppe L. Banna1

(Email: giuseppe.banna@ircc.it)

Alfredo Addeo2

(Email: alfredo.addeo@hcuge.ch)

1Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy;2Department of Oncology, Geneva University Hospitals, University of Geneva, Swiss Cancer Center Leman, Geneva, Switzerland.

Received: 17 September 2021; Accepted: 08 October 2021; Published: 30 June 2022.

doi: 10.21037/pcm-21-39

译者介绍
朱文英
女，复旦大学附属肿瘤医院肿瘤研究所生物化学与分子生物学专业博士研究生在读。本科毕业于南开大学。以共同作者的身份发表SCI论文3篇，主要进行肿瘤代谢相关的研究。（更新时间：2023-05-05）

（本译文仅供学术交流，实际内容请以英文原文为准。）

doi: 10.21037/pcm-21-39
Cite this article as: Banna GL, Addeo A. From icing to slicing the cake: the new hope of precision medicine for lung cancer. Precis Cancer Med 2022;5:11.

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