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Cancers
Volume 13
Issue 15
10.3390/cancers13153656
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Review

The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer

by
Harry B. Lengel
1,
James G. Connolly
1,
Gregory D. Jones
1,
Raul Caso
1,
Jian Zhou
2,
Francisco Sanchez-Vega
1,
Brooke Mastrogiacomo
1,
James M. Isbell
1,
Bob T. Li
3,
Yuan Liu
1,4,
Natasha Rekhtman
4,5 and
David R. Jones
1,4,*
1
Thoracic Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
2
Department of Surgery, Peking University, Beijing 100081, China
3
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4
Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Tetsuya Mitsudomi
Cancers 2021, 13(15), 3656; https://doi.org/10.3390/cancers13153656
Received: 7 June 2021 / Revised: 14 July 2021 / Accepted: 19 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)
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Simple Summary

Next-generation sequencing (NGS) has revolutionized care for patients with advanced and metastatic non-small cell lung cancer through the identification of specific oncogenic driver mutations and pairing with matched targeted therapies. The application of NGS technologies also has the potential to improve outcomes in patients with earlier-stage disease who undergo surgery as their first line of treatment. We review clinically relevant topics in this patient cohort, for whom NGS technologies have spearheaded our understanding of tumor heterogeneity, the underlying genomic features associated with lung adenocarcinoma histologic subtypes, the prediction of recurrence after surgery, the identification of minimal residual disease by circulating tumor DNA, the discernment of intrapulmonary metastases versus synchronous or metachronous disease, and the identification of patients with early-stage non-small cell lung cancer who are likely to benefit from induction or adjuvant therapies.

Abstract

During the last two decades, next-generation sequencing (NGS) has played a key role in enhancing non-small cell lung cancer treatment paradigms through the application of “targeted therapy” in advanced and metastatic disease. The use of specific tyrosine kinase inhibitors in patients with oncogenic driver alterations, such as EGFR, ALK, ROS1, BRAF V600E, MET, and NTRK mutations, among others, has changed treatment approaches and improved outcomes in patients with late-stage disease. Although NGS technology has mostly been used in the setting of systemic therapy to identify targets, response to therapy, and mechanisms of resistance, it has multiple potential applications for patients with earlier-stage disease, as well. In this review, we discuss the emerging role of NGS technologies to better understand tumor biology in patients with non-small cell lung cancer who are undergoing surgery with curative intent. In this patient cohort, we examine tumor heterogeneity, the underlying tumor genomics associated with lung adenocarcinoma subtypes, the prediction of recurrence after complete surgical resection, the use of plasma circulating tumor DNA for detection of early cancers and monitoring for minimal residual disease, the differentiation of separate primaries from intrapulmonary metastases, and the use of NGS to guide induction and adjuvant therapies. View Full-Text
Keywords: next-generation sequencing; surgery; lung cancer next-generation sequencing; surgery; lung cancer
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MDPI and ACS Style

Lengel, H.B.; Connolly, J.G.; Jones, G.D.; Caso, R.; Zhou, J.; Sanchez-Vega, F.; Mastrogiacomo, B.; Isbell, J.M.; Li, B.T.; Liu, Y.; Rekhtman, N.; Jones, D.R. The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer. Cancers 2021, 13, 3656. https://doi.org/10.3390/cancers13153656

AMA Style

Lengel HB, Connolly JG, Jones GD, Caso R, Zhou J, Sanchez-Vega F, Mastrogiacomo B, Isbell JM, Li BT, Liu Y, Rekhtman N, Jones DR. The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer. Cancers. 2021; 13(15):3656. https://doi.org/10.3390/cancers13153656

Chicago/Turabian Style

Lengel, Harry B., James G. Connolly, Gregory D. Jones, Raul Caso, Jian Zhou, Francisco Sanchez-Vega, Brooke Mastrogiacomo, James M. Isbell, Bob T. Li, Yuan Liu, Natasha Rekhtman, and David R. Jones. 2021. "The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer" Cancers 13, no. 15: 3656. https://doi.org/10.3390/cancers13153656

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