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Clinical management of metastatic colorectal cancer in the era of precision medicine.
Literature Information
| DOI | 10.3322/caac.21728 |
|---|---|
| PMID | 35472088 |
| Journal | CA: a cancer journal for clinicians |
| Impact Factor | 232.4 |
| JCR Quartile | Q1 |
| Publication Year | 2022 |
| Times Cited | 275 |
| Keywords | immunotherapy, metastatic colorectal cancer, molecular target therapy, precision medicine, tumor molecular profiling |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 0007-9235 |
| Pages | 372-401 |
| Issue | 72(4) |
| Authors | Fortunato Ciardiello, Davide Ciardiello, Giulia Martini, Stefania Napolitano, Josep Tabernero, Andres Cervantes |
TL;DR
Colorectal cancer (CRC) is a leading cause of cancer mortality, with a significant portion of patients presenting with metastatic disease, which poses challenges in management. This review highlights advances in the molecular understanding of metastatic CRC, emphasizing the importance of personalized treatment strategies through molecular stratification, ultimately improving disease control and survival, and outlining future directions for integrating comprehensive genomic and immune profiling to enhance individual therapeutic approaches.
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immunotherapy · metastatic colorectal cancer · molecular target therapy · precision medicine · tumor molecular profiling
Abstract
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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Primary Questions Addressed
- What are the specific molecular targets that have been identified for personalized treatment in metastatic colorectal cancer?
- How does the integration of host immune competence impact the clinical management strategies for patients with metastatic colorectal cancer?
- What advancements in genetic profiling have significantly influenced treatment algorithms for metastatic colorectal cancer?
- In what ways can the dynamic changes in tumor gene alterations be utilized to improve patient outcomes in metastatic colorectal cancer?
- How does the clinical management of metastatic colorectal cancer differ from that of localized colorectal cancer in the context of precision medicine?
Key Findings
Key Insights
Research Background and Objective: Colorectal cancer (CRC) is a significant health concern, accounting for around 10% of all cancers and being the second leading cause of cancer-related deaths. Metastatic colorectal cancer (mCRC) is particularly challenging, as approximately 20% of patients present with metastatic disease at diagnosis, and nearly 50% of those initially diagnosed with localized CRC will eventually develop metastases. The objective of this review is to explore advancements in the clinical management of mCRC, particularly in the context of precision medicine, which tailors treatment based on the molecular characteristics of the tumor.
Major Methods and Findings: The review discusses the progress made in understanding the molecular landscape of mCRC, which has led to the identification of various druggable molecular targets. The authors emphasize the importance of molecular stratification in guiding treatment decisions, which, while not exhaustive of the disease's complexity, represents a significant initial step towards personalized treatment. The findings indicate that personalized approaches based on genetic profiling have contributed to improved disease control and patient survival rates in mCRC. Furthermore, the authors highlight the need to integrate comprehensive knowledge of tumor genetic alterations, gene and protein expression profiles, and host immune responses into a continuum of care that adapts to the dynamic nature of the disease.
Core Conclusion: The review concludes that the future of mCRC management lies in a precision medicine framework that incorporates a deep understanding of the tumor's genetic makeup and the patient’s unique biological context. By identifying individual prognostic and predictive parameters, clinicians can tailor treatment strategies more effectively throughout the disease trajectory, ultimately improving patient outcomes.
Research Significance and Impact: This research underscores the transformative potential of precision medicine in oncology, particularly for mCRC. By moving beyond traditional treatment paradigms to a more personalized approach, there is an opportunity to significantly enhance therapeutic efficacy and patient quality of life. The integration of molecular profiling into clinical practice not only represents a shift towards more informed decision-making but also sets the stage for future innovations in cancer treatment strategies. The insights provided in this review could influence clinical guidelines and inform ongoing research efforts, leading to improved prognostic tools and therapeutic options for patients battling metastatic colorectal cancer.
Literatures Citing This Work
- 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)
- 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)
- 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)
- 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)
- 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)
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- 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)
- The Interplay between Anti-Angiogenics and Immunotherapy in Colorectal Cancer. - Brigida Anna Maiorano;Alessandro Parisi;Evaristo Maiello;Davide Ciardiello - Life (Basel, Switzerland) (2022)
- 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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