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Clinical management of metastatic colorectal cancer in the era of precision medicine. ​

文献信息 ​

DOI10.3322/caac.21728
PMID35472088
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2022
被引次数275
关键词免疫治疗、转移性结直肠癌、分子靶向治疗、精准医学、肿瘤分子剖析
文献类型Journal Article, Review, Research Support, Non-U.S. Gov't
ISSN0007-9235
页码372-401
期号72(4)
作者Fortunato Ciardiello, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Josep Tabernero, Andres Cervantes

一句话小结 ​

结直肠癌（CRC）是主要的癌症类型之一，且转移性结直肠癌（mCRC）患者的临床管理面临重大挑战。本文综述了mCRC的分子特征及其对精准医学的影响，强调通过基因分型和个性化治疗方案的应用，可以显著提高患者的生存率和疾病控制效果。

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免疫治疗 · 转移性结直肠癌 · 分子靶向治疗 · 精准医学 · 肿瘤分子剖析

摘要 ​

结直肠癌（CRC）约占所有癌症的10%，并且是癌症死亡的第二大常见原因。大约20%的患者在初始临床表现时就已为转移性结直肠癌（mCRC）。此外，局部疾病的患者中，高达50%最终会发展为转移性疾病。对这些患者的适当临床管理仍然是一个具有挑战性的医学问题。为了揭示mCRC的分子特征，已进行大量努力。这导致了几种可靶向的肿瘤分子靶点的识别，旨在为每位患者开发个性化治疗。本综述总结了在精准医学新兴时代中对mCRC患者临床管理的改善。实际上，尽管分子分层并未完全代表该疾病的复杂性，但这已成为基于当前mCRC治疗算法的第一个重要步骤，旨在进行临床上有意义的基因分型，以实施更有效的治疗方法。这导致了mCRC疾病控制和患者生存率的临床相关性提高。mCRC临床管理的下一步将是整合对肿瘤基因改变、肿瘤及微环境基因和蛋白质表达谱、宿主免疫能力的全面知识，以及将这些动态变化应用于基于精准医学的个体化护理连续体。这一方法可能会导致识别个体预后和预测参数，从而帮助临床医生在整个疾病过程中为每位mCRC患者选择最合适的治疗方案。CA癌症杂志临床版，2022；72：000-000。

英文摘要 ​

Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause of cancer deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in approximately 20% of patients. Moreover, up to 50% of patients with localized disease eventually develop metastases. Appropriate clinical management of these patients is still a challenging medical issue. Major efforts have been made to unveil the molecular landscape of mCRC. This has resulted in the identification of several druggable tumor molecular targets with the aim of developing personalized treatments for each patient. This review summarizes the improvements in the clinical management of patients with mCRC in the emerging era of precision medicine. In fact, molecular stratification, on which the current treatment algorithm for mCRC is based, although it does not completely represent the complexity of this disease, has been the first significant step toward clinically informative genetic profiling for implementing more effective therapeutic approaches. This has resulted in a clinically relevant increase in mCRC disease control and patient survival. The next steps in the clinical management of mCRC will be to integrate the comprehensive knowledge of tumor gene alterations, of tumor and microenvironment gene and protein expression profiling, of host immune competence as well as the application of the resulting dynamic changes to a precision medicine-based continuum of care for each patient. This approach could result in the identification of individual prognostic and predictive parameters, which could help the clinician in choosing the most appropriate therapeutic program(s) throughout the entire disease journey for each patient with mCRC. CA Cancer J Clin. 2022;72:000-000.

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主要研究问题 ​

  1. 在精准医学的背景下，如何评估不同分子靶点对转移性结直肠癌治疗的影响？
  2. 针对不同患者的肿瘤基因改变，个性化治疗方案的制定需要考虑哪些具体因素？
  3. 在临床管理中，如何有效整合肿瘤微环境的基因和蛋白表达特征以优化治疗策略？
  4. 如何评估患者的免疫能力在转移性结直肠癌治疗中的作用，特别是在精准医学的框架下？
  5. 针对转移性结直肠癌的个体化治疗，当前有哪些最新的临床试验或研究成果值得关注？

核心洞察 ​

  1. 研究背景和目的
    结直肠癌（CRC）约占所有癌症的10%，是癌症死亡的第二大常见原因。在约20%的患者中，结直肠癌初次临床表现为转移性结直肠癌（mCRC），而且高达50%的局部疾病患者最终会发展为转移。对于这些患者的临床管理依然是一个挑战。本文旨在总结在精准医学时代对mCRC患者临床管理的进展，特别是分子分层对个性化治疗的重要性。

  2. 主要方法和发现
    本综述回顾了mCRC的分子景观，强调了识别多种可靶向肿瘤分子靶点的努力。这些靶点的识别为开发个性化治疗方案奠定了基础。虽然目前的治疗算法基于分子分层，但尚未完全涵盖这一疾病的复杂性。这一分层策略为临床提供了基因组信息，使得在治疗方案的选择上能够更加精准，从而在疾病控制和患者生存率方面取得了显著改善。

  3. 核心结论
    精准医学的出现使得对mCRC的临床管理有了新的方向。通过综合肿瘤基因改变、肿瘤及微环境基因和蛋白质表达谱、宿主免疫能力等信息，未来的临床管理有望实现更高水平的个体化治疗。这种动态变化的应用将有助于识别个体的预后和预测参数，从而帮助临床医生在整个疾病过程中选择最合适的治疗方案。

  4. 研究意义和影响
    本研究的进展标志着精准医学在mCRC管理中的重要性，推动了对肿瘤生物学理解的深化，增强了对个体化治疗方案的实施能力。通过更有效的分子靶向治疗，患者的生存质量和生存期有望得到显著改善。此外，研究成果为未来mCRC的临床研究和治疗策略的制定提供了新的视角，促进了精准医疗在癌症治疗中的应用，为抗击CRC提供了新的希望。

引用本文的文献 ​

  1. Construction of a prognostic glycolysis-related lncRNA signature for patients with colorectal cancer. - Xinyang Zhong;Xuefeng He;Yaxian Wang;Zijuan Hu;Huixia Huang;Senlin Zhao;Hong Zhang;Ping Wei;Dawei Li - Cancer medicine (2023)
  2. CAVE-2 (Cetuximab-AVElumab) mCRC: A Phase II Randomized Clinical Study of the Combination of Avelumab Plus Cetuximab as a Rechallenge Strategy in Pre-Treated RAS/BRAF Wild-Type mCRC Patients. - Stefania Napolitano;Giulia Martini;Davide Ciardiello;Massimo Di Maio;Nicola Normanno;Antonio Avallone;Erika Martinelli;Evaristo Maiello;Teresa Troiani;Fortunato Ciardiello - Frontiers in oncology (2022)
  3. Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM). - D Ciardiello;C Chiarazzo;V Famiglietti;A Damato;C Pinto;M G Zampino;G Castellano;L Gervaso;A Zaniboni;E Oneda;S Rapisardi;R Bordonaro;C Zichi;F De Vita;M Di Maio;A Parisi;R Giampieri;R Berardi;D Lavacchi;L Antonuzzo;E Tamburini;B A Maiorano;P Parrella;T P Latiano;N Normanno;A De Stefano;A Avallone;G Martini;S Napolitano;T Troiani;E Martinelli;F Ciardiello;F De Vita;E Maiello - ESMO open (2022)
  4. Six Genes Associated with Lymphatic Metastasis in Colon Adenocarcinoma Linked to Prognostic Value and Tumor Immune Cell Infiltration. - Baoquan Wang;Changjun Yin;Xu Yang;Huibo Shi;Zheng Zhang;Jun Zhou;Peitong Zhang - Evidence-based complementary and alternative medicine : eCAM (2022)
  5. Multiple interventional embolizations for hemostasis in hemorrhage following advanced colorectal cancer treatment: a case report. - Dongqiang Yang;Bo Shi;Yazhou Li;Yu Zhao;Ping Shi;Zhigang Li - Journal of gastrointestinal oncology (2022)
  6. Application of nanotechnology in the early diagnosis and comprehensive treatment of gastrointestinal cancer. - Shenghe Deng;Junnan Gu;Zhenxing Jiang;Yinghao Cao;Fuwei Mao;Yifan Xue;Jun Wang;Kun Dai;Le Qin;Ke Liu;Ke Wu;Qianyuan He;Kailin Cai - Journal of nanobiotechnology (2022)
  7. Bio-Inorganic Layered Double Hydroxide Nanohybrids in Photochemotherapy: A Mini Review. - N Sanoj Rejinold;Goeun Choi;Jin-Ho Choy - International journal of molecular sciences (2022)
  8. Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer. - Gianluca Arrichiello;Alessandra Perrone;Stefania Napolitano;Giulia Martini;Vincenzo De Falco;Pasquale Incoronato;Maria Maddalena Laterza;Gaetano Facchini;Vincenzo Famiglietti;Valeria Nacca;Fernando Paragliola;Rossella Napolitano;Gabriella Suarato;Antonella Nicastro;Erika Martinelli;Davide Ciardiello;Fortunato Ciardiello;Teresa Troiani - Targeted oncology (2022)
  9. The Interplay between Anti-Angiogenics and Immunotherapy in Colorectal Cancer. - Brigida Anna Maiorano;Alessandro Parisi;Evaristo Maiello;Davide Ciardiello - Life (Basel, Switzerland) (2022)
  10. Real-Life Experience of the Prognostic Significance of the Primary Tumor Location on the Timing of Colorectal Liver Metastases: A Retrospective Analysis. - Carlo Signorelli;Pietro Maria Amodio;Mario Giovanni Chilelli;Roberto Santoro;Marta Schirripa;Teresa Valentina Ranalli;Gloria Pessina;Julio Rodrigo Giron Berrios;Federica Natoni;Antonella Virtuoso;Francesca Primi;Marco Mazzotta;Fabrizio Nelli;Agnese Fabbri;Eleonora Marrucci;Enzo Maria Ruggeri - Cureus (2022)

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