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
. 2016 Nov 16;15(1):73.
doi: 10.1186/s12943-016-0553-z.

Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors: guiding entry into phase I clinical trials

Yuko Tanabe  1   2   3 , Hitoshi Ichikawa  4   5 , Takashi Kohno  4 , Hiroshi Yoshida  4   6 , Takashi Kubo  4 , Mamoru Kato  7 , Satoru Iwasa  1 , Atsushi Ochiai  4   6 , Noboru Yamamoto  1 , Yasuhiro Fujiwara  2 , Kenji Tamura  8   9   10
Affiliations

Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors: guiding entry into phase I clinical trials

Yuko Tanabe et al. Mol Cancer. .

Abstract

It is still controversial whether comprehensive genome screening of target molecules by next generation sequencing (NGS) is needed to increase clinical efficacy of investigational drugs or accelerate drug development, although several studies are being carried out. Therefore, we performed a prospective study to evaluate the feasibility of comprehensive gene screening in this setting. Our findings indicate that actionable alterations were identified in 45% of the analyzed patients, most frequently in those with breast cancer. Common actionable alterations were found in PIK3CA mutation, BRCA2 mutation, ERBB2 amplification, and CCND1 amplification. In total, 22% of the analyzed patients could be entered into phase I clinical trials, and 8% of them were treated with "matched" drugs. Among patients who received matched therapies, response and disease control rates were 33 and 78%, respectively. On the other hand, in the patients who received "non-matched" therapy, the objective response rate was 6%. We believe this data indicates that NGS-based molecular pre-screening is a potent platform for use before patient entry into phase I trials.

Keywords: Driver mutation; Molecular pre-screening; Molecular targeted therapy; Next-generation sequencing; Phase I trial.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Registered and analyzed tumors in the TOPICS-1 study. The diagnoses of patients who underwent genomic testing. Each diagnosis included a variety of different histologic subtypes
Fig. 2
Fig. 2
Summary of identified genomic alterations. The mutations, amplifications and fusions observed and reported in the study
See this image and copyright information in PMC

References

    1. Ligresti G, Militello L, Steelman LS, Cavallaro A, Basile F, Nicoletti F, et al. PIK3CA mutations in human solid tumors: role in sensitivity to various therapeutic approaches. Cell Cycle. 2009;8(9):1352–8. doi: 10.4161/cc.8.9.8255. - DOI - PMC - PubMed
    1. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 2007;448(7152):439–444. doi: 10.1038/nature05933. - DOI - PubMed
    1. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10(2):116–29. doi: 10.1038/nrc2780. - DOI - PubMed
    1. Lieu C, Heymach J, Overman M, Tran H, Kopetz S. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res. 2011;17(19):6130–9. doi: 10.1158/1078-0432.CCR-11-0659. - DOI - PMC - PubMed
    1. Dienstmann R, Rodon J, Prat A, Perez-Garcia J, Adamo B, Felip E, et al. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann Oncol. 2014;25(3):552–63. doi: 10.1093/annonc/mdt419. - DOI - PMC - PubMed

Publication types