AccScience Publishing / ITPS / Volume 7 / Issue 1 / DOI: 10.36922/itps.1227
Cite this article
66
Download
745
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
REVIEW

Pharmacogenetic and liquid biopsy: The new tools of precision medicine in cancer

Verónica Alejandra Alonso1 Alberto Lazarowski1*
Show Less
1 INFIBIOC - Clinical Biochemistry Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
INNOSC Theranostics and Pharmacological Sciences 2024, 7(1), 1227 https://doi.org/10.36922/itps.1227
Submitted: 3 July 2023 | Accepted: 11 August 2023 | Published: 11 September 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

The main difficulty in the treatment of cancer lies in the already known mechanism of resistance to conventional chemotherapy. It is mainly due to the expression of the multidrug transport systems known as ABC transporters, both in neoplastic cells and in excretory organs that reduce the chemotherapeutic concentration. The cancer cell proliferation by activation of growth factor receptors induces their intrinsic tyrosine kinase activity, and their intracellular signaling pathways involved in such activation. Tumor proliferation can respond to the direct action of growth factors on their respective receptors, or due to somatic mutations in different steps of their signaling pathway, in an independent manner of growth factor stimulus. Pharmacogenetics studies have been performed to identify these drivers’ mutations and their detection enables targeted inhibitory therapies against their abnormal proteins. The design of new molecules capable of inhibiting these signals has opened a new line of treatment for each type of tumor, thereby enabling tumor growth control and giving rise to the precision medicine approach. It is possible that mutations of sensitive and resistant to these targeted therapies coexist in the same tumor, from the start of therapy or as a consequence of the first-line treatment. The mutations in circulating DNA in body fluids, which are detected and quantified by droplet digital polymerase chain reaction-assisted liquid biopsy, are the ideal biomarkers for the evaluation of pharmacological response, which is crucial for facilitating the change of therapeutic strategy involving second- or third-generation drugs. The quantification of these mutations can be used to assess minimal residual disease in the therapeutic follow-up of each case.

Keywords
Liquid biopsy
Droplet digital polymerase chain reaction
Pharmacogenetics
Somatic mutations
Sensitive mutations
Resistant mutations
Minimal residual disease
Funding
None.
References
  1. Juliano RL, Ling VA, 1976, Surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta, 455: 152–162. https://doi.org/10.1016/0005-2736(76)90160-7

 

  1. Sacha T, 2014, Imatinib in chronic myeloid leukemia: An overview. Mediterr J Hematol Infect Dis, 6: e2014007. https://doi.org/10.4084/mjhid.2014.007

 

  1. Bianchini M, De Brasi C, Gargallo P, et al., 2009, Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients. Eur J Haematol, 82: 292–300. https://doi.org/10.1111/j.1600-0609.2008.01199.x

 

  1. Pagnano KB, Bendit I, Boquimpani C, et al., 2015, BCR-ABL mutations in chronic myeloid leukemia treated with tyrosine kinase inhibitors and impact on survival. Cancer Invest, 33: 451–458. https://doi.org/10.3109/07357907.2015.1065499

 

  1. Awidi A, Ababneh N, Magablah A, et al., 2012, ABL kinase domain mutations in patients with chronic myeloid leukemia in Jordan. Genet Test Mol Biomarkers, 16: 1317–1321. https://doi.org/10.1089/gtmb.2012.0147

 

  1. Haddad FG, Issa GC, Jabbour E, et al., 2022, Ponatinib for the treatment of adult patients with resistant or intolerant Chronic-phase Chronic Myeloid Leukemia. Expert Opin Pharmacother, 23: 751–758. https://doi.org/10.1080/14656566.2022.2064742

 

  1. Hoffmeyer S, Burk O, von Richter O, et al., 2000, Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A, 97: 3473–3478. https://doi.org/10.1073/pnas.97.7.3473

 

  1. Lardo M, Castro M, Moiraghi B, et al., 2015, MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia. Blood Res, 50: 154–159. https://doi.org/10.5045/br.2015.50.3.154

 

  1. Pieri L, Spolverini A, Scappini B, et al., 2011, Concomitant occurrence of BCR-ABL and JAK2V617F mutation. Blood, 118: 3445–3446. https://doi.org/10.1182/blood-2011-07-365007

 

  1. Zhou A, Knoche EM, Engle EK, et al., 2015, Concomitant JAK2 V617F-positive polycythemia vera and BCR-ABL-positive chronic myelogenous leukemia treated with ruxolitinib and dasatinib. Blood Cancer J, 5: e351. https://doi.org/10.1038/bcj.2015.77

 

  1. Fry DW, Kraker AJ, McMichael A, et al., 1994, A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science, 265: 1093–1095. https://doi.org/10.1126/science.8066447

 

  1. Ward WH, Cook PN, Slater AM, et al., 1994, Epidermal growth factor receptor tyrosine kinase. Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor. Biochem Pharmacol, 48: 659–666. https://doi.org/10.1016/0006-2952(94)90042-6

 

  1. Osherov N, Levitzki A, 1994, Epidermal-growth-factor-dependent activation of the src-family kinases. Eur J Biochem, 225: 1047–1053. https://doi.org/10.1111/j.1432-1033.1994.1047b.x

 

  1. Laface C, Maselli FM, Santoro AN, et al., 2023, The resistance to EGFR-TKIs in non-small cell lung cancer: From molecular mechanisms to clinical application of new therapeutic strategies. Pharmaceutics, 15: 1604. https://doi.org/10.3390/pharmaceutics15061604

 

  1. Zhang SS, Nagasaka M, 2021, Spotlight on sotorasib (AMG 510) for KRAS G12C positive non-small cell lung cancer. Lung Cancer (Auckl), 12: 115–122. https://doi.org/10.2147/lctt.s334623

 

  1. Wee P, Wang Z, 2017, Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel), 9: 52. https://doi.org/10.3390/cancers9050052

 

  1. Miyamoto Y, Suyama K, Baba H, 2017, Recent advances in targeting the EGFR signaling pathway for the treatment of metastatic colorectal cancer. Int J Mol Sci, 18: 752. https://doi.org/10.3390/ijms18040752

 

  1. Ulz P, Belic J, Graf R, et al., 2016, Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer. Nat Commun, 7: 12008. https://doi.org/10.1038/ncomms12008

 

  1. Yamaoka T, Ohba M, Ohmori T, 2017, Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms. Int J Mol Sci, 18: 2420. https://doi.org/10.3390/ijms18112420

 

  1. Sigismund S, Avanzato D, Lanzetti L, 2018, Emerging functions of the EGFR in cancer. Mol Oncol, 12: 3–20. https://doi.org/10.1002/1878-0261.12155

 

  1. An L, Wang Y, Wu G, et al., 2023, Defining the sensitivity landscape of EGFR variants to tyrosine kinase inhibitors. Transl Res, 255: 14–25. https://doi.org/10.1016/j.trsl.2022.11.002

 

  1. Hasenahuer MA, Parisi G, Gautier M, et al., 2015, Twenty-one novel EGFR kinase domain variants in patients with nonsmall cell lung cancer. Ann Hum Genet, 79: 385–393. https://doi.org/10.1111/ahg.12127

 

  1. Chen D, Li L, Zhang X, et al., 2018, FOLFOX plus anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is an effective first-line treatment for patients with RAS-wild left-sided metastatic colorectal cancer: A meta-analysis. Medicine (Baltimore), 97: e0097. https://doi.org/10.1097/MD.0000000000010097

 

  1. Matsuhashi N, Takahashi T, Matsui S, et al., 2018, A novel therapeutic strategy of personalized medicine based on anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer. Int J Oncol, 52: 1391–1400. https://doi.org/10.3892/ijo.2018.4322

 

  1. Gazdar AF, Minna JD, 2005, Inhibition of EGFR signaling: All mutations are not created equal. PLoS Med, 2: e377. https://doi.org/10.1371/journal.pmed.0020377

 

  1. Shigematsu H, Gazdar AF, 2006, Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer, 118: 257–262. https://doi.org/10.1002/ijc.21496

 

  1. Sanders HR, Albitar M, 2010, Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet, 203: 7–15. https://doi.org/10.1016/j.cancergencyto.2010.07.134

 

  1. Mésange P, Bouygues A, Ferrand N, et al., 2018, Combinations of bevacizumab and erlotinib show activity in colorectal cancer independent of RAS status. Clin Cancer Res, 24: 2548–2558. https://doi.org/10.1158/1078-0432.ccr-17-3187

 

  1. Dankner M, Rose AA, Rajkumar S, et al., 2018, Classifying BRAF alterations in cancer: New rational therapeutic strategies for actionable mutations. Oncogene, 37: 3183–3199. https://doi.org/10.1038/s41388-018-0171-x

 

  1. Maitre E, Bertrand P, Maingonnat C, et al., 2018, New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes. Oncotarget, 9: 28866–28876. https://doi.org/10.18632/oncotarget.25601

 

  1. Kamps R, Brandão RD, van den Bosch BJ, et al., 2017, Next-generation sequencing in oncology: Genetic diagnosis, risk prediction and cancer classification. Int J Mol Sci, 18: 308. https://doi.org/10.3390/ijms18020308

 

  1. Lehmann-Che J, Poirot B, Boyer JC, et al., 2017, Cancer genomics guide clinical practice in personalized medicine. Therapie, 72: 439–451. https://doi.org/10.1016/j.therap.2016.09.015

 

  1. Galetti M, Petronini PG, Fumarola C, et al., 2015, Effect of ABCG2/BCRP expression on efflux and uptake of gefitinib in NSCLC cell lines. PLoS One, 10: e0141795. https://doi.org/10.1371/journal.pone.0141795

 

  1. Shukla S, Patel A, Ambudkar SV, 2016, Mechanistic and pharmacological insights into modulation of ABC drug transporters by tyrosine kinase inhibitors. In: George AM, editor. ABC Transporters-40 Years On. Switzerland: Springer International Publishing, p227.

 

  1. Vietsch EE, van Eijck CH, Wellstein A, 2015, Circulating DNA and micro-RNA in patients with pancreatic cancer. Pancreat Disord Ther, 5: 156. https://doi.org/10.4172/2165-7092.1000156

 

  1. Azad AA, Volik SV, Wyatt AW, et al., 2015, Androgen receptor gene aberrations in circulating cell-free DNA: Biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res, 21: 2315–2324. https://doi.org/10.1158/1078-0432.CCR-14-2666

 

  1. Heitzer E, Perakis S, Geigl JB, et al., 2017, The potential of liquid biopsies for the early detection of cancer. NPJ Precis Oncol, 1: 36. https://doi.org/10.1038/s41698-017-0039-5

 

  1. De Kock R, van den Borne B, Youssef-El Soud M, et al., 2021, Therapy monitoring of EGFR-positive non-small-cell lung cancer patients using ddPCR multiplex assays. J Mol Diagn, 23: 495–505. https://doi.org/10.1016/j.jmoldx.2021.01.003

 

  1. Rolfo C, Castiglia M, Hong D, et al., 2014, Liquid biopsies in lung cancer: The new ambrosia of researchers. Biochim Biophys Acta, 1846: 539–546. https://doi.org/10.1016/j.bbcan.2014.10.001

 

  1. Diaz LA Jr., Bardelli A, 2014, Liquid biopsies: Genotyping circulating tumor DNA. J Clin Oncol, 32: 579–586. https://doi.org/10.1200/jco.2012.45.2011

 

  1. Montagut C, Argilés G, Ciardiello F, et al., 2018, Efficacy of Sym004 in patients with metastatic colorectal cancer with acquired resistance to anti-EGFR therapy and molecularly selected by circulating tumor DNA analyses: A phase 2 randomized clinical trial. JAMA Oncol, 4: e175245. https://doi.org/10.1001/jamaoncol.2017.5245
Conflict of interest
The authors have no conflict of interest.
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing