Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan;23(1):65-69.
doi: 10.7861/clinmed.2022-0514.

Next-generation sequencing and molecular therapy

Affiliations

Next-generation sequencing and molecular therapy

Cienne Morton et al. Clin Med (Lond). 2023 Jan.

Abstract

Cancers contain a plethora of mutations, few of which are critical to maintaining a state of malignancy. With our ever-expanding understanding of the genomic complexity of cancer, potentially actionable biomarkers whose inhibition could cripple cancer growth are increasingly being elucidated. Modern cancer drug development has largely switched from cytotoxic agents to targeted therapies and immunotherapy, with noteworthy success in several cancer types including non-small-cell lung cancer (NSCLC), breast cancer and melanoma. Next-generation sequencing offers high-throughput, widescale genomic interrogation in a far more efficient and affordable manner than previous sequencing methods. This facilitates detection of potentially actionable mutations and fusions for individual patients and contributes to the identification of novel predictive and prognostic biomarkers in a population. Challenges in the technical aspects of biopsy and sequencing, interpretation, and development of targeted therapies against common genomic aberrations will need to be addressed for personalised medicine to become a reality for more patients with cancer.

Keywords: cancer genomics; liquid biopsy; nextgeneration sequencing; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

C Morton has received honoraria from MSD. D Sarker reports personal fees for honoraria/advisory boards/consulting from MSD, Bayer, Eisai, AstraZeneca, Surface Oncology, Sirtex Medical, Roche, and AAA; nonfinancial support from MiNA Therapeutics and Medivir; and grants from UCB and Inspirata. P Ross reports personal fees for honoraria/advisory boards/consulting from Amgen, AstraZeneca, Eisai, Merck, Sirtex Medical, Boston Scientific, Roche, Servier. Non-financial support from HMP Education and Oncosil and grants from Sanofi and Sirtex medical.

References

    1. Robert C, Grob JJ, Stroyakovskiy D, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381:626–636. - PubMed
    1. Soria J, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113–125. - PubMed
    1. National Institute for Health and Care Excellence . NICE; London: 2020. Larotrectinib for treating NTRK fusion-positive solid tumours. Guidance.
    1. Anandakrishnan R, Varghese RT, Kinney NA, Garner HR. Estimating the number of genetic mutations (hits) required for carcinogenesis based on the distribution of somatic mutations. PLoS Comput Biol. 2019;15:e1006881. - PMC - PubMed
    1. Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 2022;33:929–938. - PubMed

Uncited References

    1. Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381:338–348. - PubMed

Substances