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Tumor Discovery                                                     CTC characterization for EGFR mutations



            the two previous studies. 66,67  Both these studies proposed   Writing – review & editing:  Micheal J. Lind, John
            that the discordance in mutations between CTCs and   Greenman
            tumor biopsies may be due to the heterogeneity of tumors
            as discussed above. The apparent discordance in mutations   Ethics approval and consent to participate
            observed in CTCs and tumor biopsies will need to be   The study adhered to the REMARK guidelines. It was
            further investigated  using approaches for  CTC  isolation   conducted at the Queens Centre for Oncology and
            and downstream analysis that properly define mutations   Hematology, Castle Hill Hospital, Hull, in collaboration
            derived from single cells or multiple cell clones.  with the Centres for Biomedicine and Clinical Sciences
            5. Conclusion                                      at the University of Hull, United  Kingdom. The North
                                                               East-Newcastle & North Tyneside Local Research Ethics
            The results obtained from this study suggest that the new   Committee approved this study (REC13/NE/0242). In
            microfluidic device described can be used to isolate CTCs   accordance with the Declaration of Helsinki, informed
            for downstream mutational analysis of  EGFR mutations.   consent was obtained in written form from all participants.
            The device was able to isolate EpCAM-expressing PC-9 cell
            lines and EpCAM-positive CTCs from media and blood,   Consent for publication
            respectively, with the isolated EpCAM-positive cells having   Consent in written form was obtained from participants in
            been successfully analyzed for mutations in the EGFR gene.   the study to publish their data.
            The mutational profile obtained from CTCs for the recruited
            patients has positive clinical implications as it indicates   Availability of data
            that a single blood draw may be able to provide a snapshot   The data from this study can be obtained on request from
            of molecular events in a malignancy from initiation to
            metastasis. However, the current study is limited by the   the senior author, Prof J. Greenman.
            sample size. Hence, it is our intention to carry out further   References
            studies in a larger cohort to better evaluate the utility of
            this technology and make the necessary modifications for   1.   Rajadurai P, Yap NY, Mohamed Yousoof SB, Cheah YK.
            translation into clinical practice. Furthermore, we intend to   Mutational profiling of lung cancer using next generation
            analyze different methods for the genomic analysis of CTCs   sequencing: A  Malaysian real-world clinical diagnostic
                                                                  experience. J Mol Pathol. 2023;4(1):31-43.
            to define mutations in single cells.
                                                                  doi: 10.3390/jmp4010004
            Acknowledgments                                    2.   Petrelli F, Borgonovo K, Cabiddu M, Barni S. Efficacy of

            The authors are grateful to colleagues at the STAB VIDA,   EGFR tyrosine kinase inhibitors in patients with EGFR-
            Portugal for help with next-generation sequencing,    mutated non-small-cell lung cancer: A meta-analysis of 13
            Dr.  Alex Iles (Department of Chemistry, University of   randomized trials. Clin Lung Cancer. 2012;13(2):107-114.
            Hull) for chip design and manufacture, and Dr. Emmanuel      doi: 10.1016/j.cllc.2011.08.005
            Nna of Biosystem Laboratories, Bedford, United Kingdom   3.   Petrella F, Rizzo S, Attili I,  et al. Stage III non-small-cell
            for help with bioinformatics analysis.                lung cancer: An overview of treatment options. Curr Oncol.

            Funding                                               2023;30(3):3160-3175.
                                                                  doi: 10.3390/curroncol30030239
            The travel and consumable costs related to this work were
            supported by the EU/Marie Curie  Lung Card project   4.   Robichaux JP, Le X, Vijayan RSK,  et al. Structure-based
            (No. 734790) and Yorkshire Cancer Research (H395).    classification predicts drug response in EGFR-mutant
                                                                  NSCLC. Nature. 2021;597(7878):732-737.
            Conflict of interest                                  doi: 10.1038/s41586-021-03898-1
            The authors declare that they have no competing interests.  5.   Sasaki A, Fujimoto Y., Inada T,  et al. Efficacy of tyrosine
                                                                  kinase inhibitors in patients with non-small-cell lung cancer
            Author contributions                                  with performance status 4: A case series and review of the
                                                                  literature. J Med Case Rep. 202;17(1):410.
            Conceptualization: John Greenman, Micheal J. Lind
            Formal analysis: Nkeiruka O. Ogidi, John Greenman      doi: 10.1186/s13256-023-04145-z
            Investigation: Nkeiruka O. Ogidi                   6.   Russo A, Franchina T, Ricciardi G, Picciotto M, Adamo  V.
            Methodology: Nkeiruka O. Ogidi, John Greenman         Heterogeneous responses to epidermal growth factor
            Writing – original draft: Nkeiruka O. Ogidi           receptor (EGFR) tyrosine kinase inhibitors (TKIs) in


            Volume 3 Issue 4 (2024)                         13                                doi: 10.36922/td.3987
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