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Аннотация
Концентрация циркулирующих опухолевых ДНК (цоДНК) в крови является чувствительным и специфичным маркером для мониторинга в режиме реального времени динамики опухолевой массы. Количественный анализ цоДНК дает возможность оценить ответ опухоли на терапию на самых ранних этапах воздействия, а неинвазивный характер подобной процедуры («жидкостной биопсии») делает ее незаменимой в случаях малой доступности и множественности опухолевых очагов. Важно, что изменение спектра «циркулирующих» мутаций достаточно полно отражает эволюцию неопластических клонов и механизмы молекулярной адаптации клеток к воздействию препаратов — эта информация крайне ценна для своевременной коррекции терапевтической схемы на стадиях, предшествующих клинической манифестации прогрессирования. Многочисленные клинические испытания динамики цоДНК у пациентов, получающих таргетные или химиотерапевтические препараты, продемонстрировали как прогностическую, так и предиктивную ценность данного подхода. Эти усилия подчеркивают растущую роль жидкостной биопсии при выборе тактики на всех этапах лечения с момента постановки диагноза: в отборе пациентов для таргетной или иммунотерапии терапии на основании молекулярных свойств опухоли, мониторинге эффективности препаратов, определении оптимальной продолжительности терапии, диагностике рецидивов. Данный обзор суммирует накопленные к настоящему моменту сведения об успехах и ограничениях использования цоДНК в роли клинически значимого экспресс-маркера для оценки эффективности противоопухолевой терапии на примере основных онкологических локализаций: рака толстой кишки, рака легкого, рака молочной железы, яичника, простаты и т. д.
Библиографические ссылки
Thierry AR, El Messaoudi S, Gahan PB, et al. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016;35(3):347-376. https://doi.org/10.1007/s10555-016-9629-x.
Caputo V, Ciardiello F, Corte CMD, et al. Diagnostic value of liquid biopsy in the era of precision medicine: 10 years of clinical evidence in cancer. Explor Target Antitumor Ther. 2023;4:102-138. https://doi.org/10.37349/etat.2023.00125.
García-Silva S, Gallardo M, Peinado H. DNA-Loaded extracellular vesicles in liquid biopsy: Tiny players with big potential? Front Cell Dev Biol. 2021;8:622579. https://doi.org/10.3389/fcell.2020.622579.
Lanman RB, Mortimer SA, Zill OA, et al. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS One. 2015;10(10):e0140712. https://doi.org/10.1371/journal.pone.0140712.
Elazezy M, Joosse SA. Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management. Comput Struct Biotechnol J. 2018;16:370-378. https://doi.org/10.1016/j.csbj.2018.10.002.
van der Pol Y, Mouliere F. Toward the early detection of cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA. Cancer Cell. 2019;36:350-368. https://doi.org/10.1016/j.ccell.2019.09.003.
Cervena K, Vodicka P, Vymetalkova V. Diagnostic and prognostic impact of cell-free DNA in human cancers: Systematic review. Mutat Res Rev Mutat Res. 2019;781:100-129. https://doi.org/10.1016/j.mrrev.2019.05.002.
Kuligina ES, Meerovich R, Zagorodnev KA, et al. Content of circulating tumor DNA depends on the tumor type and the dynamics of tumor size, but is not influenced significantly by physical exercise, time of the day or recent meal. Cancer Genet. 2021;256-257:165-178. https://doi.org/10.1016/j.cancergen.2021.05.014.
Stejskal P, Goodarzi H, Srovnal J, et al. Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance. Mol Cancer. 2023;22(1):15. https://doi.org/10.1186/s12943-022-01710-w.
Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24. https://doi.org/10.1126/scitranslmed.3007094.
C Choi JJ, Reich CF 3rd, Pisetsky DS. The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunology. 2005;115(1):55-62. https://doi.org/10.1111/j.1365-2567.2005.02130.x.
Nguyen VC, Nguyen TH, Phan TH, et al. Fragment length profiles of cancer mutations enhance detection of circulating tumor DNA in patients with early-stage hepatocellular carcinoma. BMC Cancer. 2023;23(1):233. https://doi.org/10.1186/s12885-023-10681-0.
Qi T, Pan M, Shi H, et al. Cell-Free DNA fragmentomics: The novel promising biomarker. Int J Mol Sci. 2023;24(2):1503. https://doi.org/10.3390/ijms24021503.
Avanzini S, Kurtz DM, Chabon JJ, et al. A mathematical model of ctDNA shedding predicts tumor detection size. Sci Adv. 2020;6:eabc4308. https://doi.org/10.1126/sciadv.abc4308.
Kustanovich A, Schwartz R, Peretz T, et al. Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20:1057-1067. https://doi.org/10.1080/15384047.2019.1598759.
Khier S, Lohan L. Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature. Future Sci OA. 2018;4(4):FSO295. https://doi.org/10.4155/fsoa-2017-0140.
Calapre L, Giardina T, Beasley AB, et al. Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies. Sci Rep. 2023;13:278. https://doi.org/10.1038/s41598-023-27445-2.
Bonner ER, Harrington R, Eze A, et al. Circulating tumor DNA sequencing provides comprehensive mutation profiling for pediatric central nervous system tumors. NPJ Precis Oncol. 2022;6:63. https://doi.org/10.1038/s41698-022-00306-3.
Shah AT, Azad TD, Breese MR, et al. A comprehensive circulating tumor DNA assay for detection of translocation and copy-number changes in pediatric sarcomas. Mol Cancer Ther. 2021;20:2016-2025. https://doi.org/10.1158/1535-7163.MCT-20-0987.
Hai L, Li L, Liu Z, et al. Whole-genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer. MedComm (2020). 2022;3(3):e134. https://doi.org/10.1002/mco2.134.
Foda ZH, Annapragada AV, Boyapati K, et al. detecting liver cancer using cell-free DNA fragmentomes. Cancer Discov. 2023;13:616-631. https://doi.org/10.1158/2159-8290.CD-22-0659.
Shtumpf M, Piroeva KV, Agrawal SP, et al. NucPosDB: a database of nucleosome positioning in vivo and nucleosomics of cell-free DNA. Chromosoma. 2022;131(1-2):19-28. https://doi.org/10.1007/s00412-021-00766-9.
Li L, Yeh H, Chen J. Circulating virus–host chimera DNAs in the clinical monitoring of virus-related cancers. Cancers. 2022;14(10). https://doi.org/10.3390/cancers14102531.
Huang F, Yang Y, Chen X, et al. Chemotherapy-associated clonal hematopoiesis mutations should be taken seriously in plasma cell-free DNA KRAS/NRAS/BRAF genotyping for metastatic colorectal cancer. Clin Biochem. 2021;92:46-53. https://doi.org/10.1016/j.clinbiochem.2021.03.005.
Chan HT, Chin YM, Nakamura Y, et al. Clonal hematopoiesis in liquid biopsy: From biological noise to valuable clinical implications. Cancers (Basel). 2020;12:2277. https://doi.org/10.3390/cancers12082277.
Sanz-Garcia E, Zhao E, Bratman SV, et al. Monitoring and adapting cancer treatment using circulating tumor DNA kinetics: Current research, opportunities, and challenges. Sci Adv. 2022;8:eabi8618. https://doi.org/10.1126/sciadv.abi8618.
Parkinson CA, Gale D, Piskorz AM, et al. Exploratory analysis of TP53 mutations in circulating tumour DNA as biomarkers of treatment response for patients with relapsed high-grade serous ovarian carcinoma: A retrospective study. PLoS Med. 2016;13(12):e1002198. https://doi.org/10.1371/journal.pmed.1002198.
Kruger S, Heinemann V, Ross C, et al. Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer. Ann Oncol. 2018;29:2348-2355. https://doi.org/10.1093/annonc/mdy417.
Patsch K, Matasci N, Soundararajan A, et al. Monitoring dynamic cytotoxic chemotherapy response in castration-resistant prostate cancer using plasma cell-free DNA (cfDNA). BMC Res Notes. 2019;12:275. https://doi.org/10.1186/s13104-019-4312-2.
Moser T, Waldispuehl-Geigl J, Belic J, et al. On-treatment measurements of circulating tumor DNA during FOLFOX therapy in patients with colorectal cancer. NPJ Precis Oncol. 2020;4:30. https://doi.org/10.1038/s41698-020-00134-3.
Callesen LB, Hamfjord J, Boysen AK, et al. Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis. Br J Cancer. 2022;127:500-513. https://doi.org/10.1038/s41416-022-01816-4.
Tie J, Kinde I, Wang Y, et al. Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol. 2015;26(8):1715-22. https://doi.org/10.1093/annonc/mdv177.
Krumbholz M, Hellberg J, Steif B, et al. Genomic EWSR1 fusion sequence as highly sensitive and dynamic plasma tumor marker in ewing sarcoma. Clin Cancer Res. 2016;22:4356-4365. https://doi.org/10.1158/1078-0432.CCR-15-3028.
Hrebien S, Citi V, Garcia-Murillas I, et al. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol. 2019;30:945-952. https://doi.org/10.1093/annonc/mdz085.
Magbanua MJM, Swigart LB, Wu HT, et al. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2021;32:229-239. https://doi.org/10.1016/j.annonc.2020.11.007.
Parikh AR, Mojtahed A, Schneider JL, et al. Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers. Clin Cancer Res. 2020;26:1877–1885. https://doi.org/10.1158/1078-0432.CCR-19-3467.
Alvarez J, Cercek A, Mohan N, et al. Circulating tumor DNA (ctDNA) for response assessment in patients with anal cancer treated with definitive chemoradiation. J Clin Oncol. 2023;41(4 suppl):1–1. https://doi.org/10.1200/JCO.2023.41.4_suppl.1.
Moati E, Blons H, Taly V, et al. Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer. Int J Cancer. 2020;147(4):1185-1189. https://doi.org/10.1002/ijc.32657.
Perets R, Greenberg O, Shentzer T, et al. Mutant KRAS circulating tumor DNA is an accurate tool for pancreatic cancer monitoring. Oncologist. 2018;23:566–572. https://doi.org/10.1634/theoncologist.2017-0467.
Cremolini C, Rossini D, Dell'Aquila E, et al. Rechallenge for patients with RAS and BRAF wild-type metastatic colorectal cancer with acquired resistance to first-line Cetuximab and Irinotecan: A phase 2 single-arm clinical trial. JAMA Oncol. 2019;5:343-350. https://doi.org/10.1001/jamaoncol.2018.5080.
Wei T, Zhang Q, Li X, et al. Monitoring tumor burden in response to FOLFIRINOX chemotherapy via profiling circulating cell-free DNA in pancreatic cancer. Mol. Cancer Ther. 2019;18:196-203. https://doi.org/10.1158/1535-7163.MCT-17-1298.
Almodovar K, Iams WT, Meador CB, et al. Longitudinal cell-free DNA analysis in patients with small cell lung cancer reveals dynamic insights into treatment efficacy and disease relapse. J Thorac Oncol. 2018;13:112-123. https://doi.org/10.1016/j.jtho.2017.09.1951.
Osumi H, Shinozaki E, Yamaguchi K, et al. Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer. Sci Rep. 2019;9:17358. https://doi.org/10.1038/s41598-019-53711-3.
Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol. 2018;36:2845-2853. https://doi.org/10.1200/JCO.2018.78.5246.
Raunkilde L, Hansen TF, Andersen RF, et al. NPY gene methylation in circulating tumor DNA as an early biomarker for treatment effect in metastatic colorectal cancer. Cancers (Basel). 2022;14:4459. https://doi.org/10.3390/cancers14184459.
Lupo J, Truffot A, Andreani J, et al. Virological markers in Epstein-Barr virus-associated diseases. Viruses. 2023;15(3):656. https://doi.org/10.3390/v15030656.
Moiseyenko FV, Kuligina ES, Zhabina AS, et al. Changes in the concentration of EGFR-mutated plasma DNA in the first hours of targeted therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer. Int J Clin Oncol. 2022;27:850-862. https://doi.org/10.1007/s10147-022-02128-6.
Riediger AL, Dietz S, Schirmer U, et al. Mutation analysis of circulating plasma DNA to determine response to EGFR tyrosine kinase inhibitor therapy of lung adenocarcinoma patients. Sci Rep. 2016;6:33505. https://doi.org/10.1038/srep33505.
Schreuer M, Meersseman G, van Den Herrewegen S, et al. Applications for quantitative measurement of BRAF V600 mutant cell-free tumor DNA in the plasma of patients with metastatic melanoma. Melanoma Res. 2016;26(2):157-63. https://doi.org/10.1097/CMR.0000000000000224.
He J, Tan W, Tang X, et al. Variations in EGFR ctDNA correlates to the clinical efficacy of Afatinib in non-small cell lung cancer with acquired resistance. Pathol Oncol Res. 2017;23:307-315. https://doi.org/10.1007/s12253-016-0097-y.
Taus Á, Camacho L, Rocha P, et al. Dynamics of EGFR mutation load in plasma for prediction of treatment response and disease progression in patients with EGFR-mutant lung adenocarcinoma. Clin Lung Cancer. 2018;19:387-394.e2. https://doi.org/10.1016/j.cllc.2018.03.015.
Zhou Q, Yang JJ, Chen ZH, et al. Serial cfDNA assessment of response and resistance to EGFR-TKI for patients with EGFR-L858R mutant lung cancer from a prospective clinical trial. J Hematol Oncol. 2016;9(1):86. https://doi.org/10.1186/s13045-016-0316-8.
Kato K, Uchida J, Kukita Y, et al. Numerical indices based on circulating tumor DNA for the evaluation of therapeutic response and disease progression in lung cancer patients. Sci Rep. 2016;6:29093. https://doi.org/10.1038/srep29093.
O'Leary B, Hrebien S, Morden JP, et al. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat Commun. 2018;9:896. https://doi.org/10.1038/s41467-018-03215-x.
Passiglia F, Rizzo S, Di Maio M, et al. The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M mutation in NSCLC: a systematic review and meta-analysis. Sci Rep. 2018;8:13379. https://doi.org/10.1038/s41598-018-30780-4.
Dal Maso A, Del Bianco P, Cortiula F, et al. EGFR T790M testing through repeated liquid biopsy over time: a real-world multicentric retrospective experience. J Thorac Dis. 2022;14(9):3364-3375. https://doi.org/10.21037/jtd-22-745.
Heitzer E, van den Broek D, Denis MG, et al. Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer. ESMO Open. 2022;7(2):100399. https://doi.org/10.1016/j.esmoop.2022.100399.
Jin H, Wang L, Bernards R. Rational combinations of targeted cancer therapies: background, advances and challenges. Nat Rev Drug Discov. 2023;22(3):213-234. https://doi.org/10.1038/s41573-022-00615-z.
Yaeger R, Mezzadra R, Sinopoli J, et al. Molecular characterization of acquired resistance to KRASG12C-EGFR inhibition in colorectal cancer. Cancer Discov. 2023;13:41-55. https://doi.org/10.1158/2159-8290.CD-22-0405.
Christenson ES, Lim SJ, Durham J, et al. Cell-free DNA predicts prolonged response to multiagent chemotherapy in pancreatic ductal adenocarcinoma. Cancer Res Commun. 2022;2:1418-1425. https://doi.org/10.1158/2767-9764.CRC-22-0343.
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