Login Register Cart 0
Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Systematic Review Article

Pharmacogenomics: Importance in Exploration of Target Molecule, Drug Resistance and Mechanism in Cancer Chemotherapy

Author(s): Pooja Kumari and Anandkumar Tengli*

Volume 21, Issue 1, 2024

Published on: 16 April, 2024

Page: [2 - 16] Pages: 15

DOI: 10.2174/0118756921288305240408084708

Price: $65

Abstract

Background: The field of pharmacogenomics investigates the ways in which genes impact the body's reaction to drugs. Through the integration of genetics and medical knowledge, it is possible to develop individualised and efficient therapies that are based on genetic profiles. Specifically, this evaluation focuses on three aspects: 1) Finding molecular targets and gaining a grasp of their structures is the first step. 2) Using pharmacogenomics to lessen the harmful effects of drugs 1. 3) Predicting pharmacological mechanisms based on genetic variances.

Methods: A systematic review examining pharmacogenomics' role in cancer chemotherapy, focusing on target molecules, drug resistance, and mechanism, was conducted using PRISMA-compliant databases. The review included English-published journals from 2000-2023, aiming to reduce bias and ensure all relevant research is found, chosen, and critically assessed.

Results: The results show that over the past 20 years, cytotoxic medications and personalized treatments have significantly improved cancer treatment strategies. Targeted drugs, small molecule drugs, and pharmacogenomic biomarkers offer targeted treatment for carcinoma tissues.

Conclusion: Understanding genetic profiles and drug resistance is crucial for effective cancer treatment. Combination therapies have advanced treatment for advanced or metastatic cancers.

« Previous Next »
Graphical Abstract

[1]
Russell C, Rahman A, Mohammed AR. Application of genomics, proteomics and metabolomics in drug discovery, development and clinic. Ther Deliv 2013; 4(3): 395-413.
[http://dx.doi.org/10.4155/tde.13.4] [PMID: 23442083]
[2]
Abrahams E, Silver M. The case for personalized medicine. J Diab Sci Technol 2009; 3(4): 680-4.
[http://dx.doi.org/10.1177/193229680900300411 ] [PMID: 20144313]
[3]
What is pharmacogenomics? Available from: https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/#:~:text=Pharmacogenomics%20is%20the%20story%20of,on%20a%20
[4]
Pirmohamed M. Pharmacogenomics: Current status and future perspectives. Nat Rev Genet 2023; 24(6): 350-62.
[http://dx.doi.org/10.1038/s41576-022-00572-8 ] [PMID: 36707729]
[5]
Cayún JP, Quiñones LA. Current status of cancer pharmacogenomics. In: Precision medicine for investigators, practitioners and providers. Academic Press 2020; pp. 233-43.
[http://dx.doi.org/10.1016/B978-0-12-819178-1.00022-8]
[6]
Zhang G, Nebert DW. Personalized medicine: Genetic risk prediction of drug response. Pharmacol Ther 2017; 175: 75-90.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.036 ] [PMID: 28213088]
[7]
Burki TK. Defining precision medicine. Lancet Oncol 2017; 18(12): e719.
[http://dx.doi.org/10.1016/S1470-2045(17)30865-3 ] [PMID: 29153736]
[8]
Vicente RAE, Lumbreras E, Hernández JM, et al. Pharmacogenetics and pharmacogenomics as tools in cancer therapy. Drug Metab Pers Ther 2016; 31(1): 25-34.
[http://dx.doi.org/10.1515/dmpt-2015-0042 ] [PMID: 26863347]
[9]
Sadee W, Wang D, Hartmann K, Toland AE. Pharmacogenomics: Driving personalised medicine. Pharmacol Rev 2023; 75(4): 789-814.
[http://dx.doi.org/10.1124/pharmrev.122.000810 ] [PMID: 36927888]
[10]
Sanoudou D, Mountzios G, Arvanitis DA, Pectasides D. Array-based pharmacogenomics of molecular-targeted therapies in oncology. Pharmacogenomics J 2012; 12(3): 185-96.
[http://dx.doi.org/10.1038/tpj.2011.53] [PMID: 22249357]
[11]
Feng X, Brazil B, Pearson D. Therapeutic application of pharmacogenomics in oncology: Selective biomarkers for cancer treatment. US Pharm 2011; 36(11): 5-12.
[12]
Zhang Y, Somtakoune SD, Cheung C, Listiawan M, Feng X. Therapeutic application of pharmacogenomics in oncology. AAPS J 2016; 18(4): 819-29.
[http://dx.doi.org/10.1208/s12248-016-9926-x ] [PMID: 27178043]
[13]
Wilkes GM. Targeted therapy: Attacking cancer with molecular and immunological targeted agents. Asia Pac J Oncol Nurs 2018; 5(2): 137-55.
[http://dx.doi.org/10.4103/apjon.apjon_79_17 ] [PMID: 29607374]
[14]
Lee YT, Tan YJ, Oon CE. Molecular targeted therapy: Treating cancer with specificity. Eur J Pharmacol 2018; 834: 188-96.
[http://dx.doi.org/10.1016/j.ejphar.2018.07.034 ] [PMID: 30031797]
[15]
Zhong L, Li Y, Xiong L, et al. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct Target Ther 2021; 6(1): 201.
[http://dx.doi.org/10.1038/s41392-021-00572-w ] [PMID: 34054126]
[16]
Streeter OE Jr. Precision medicine: A multidisciplinary approach. Clin Collect 2020; 8: 29-37.
[17]
Kim JA, Ceccarelli R, Lu CY. Pharmacogenomic biomarkers in US FDA-approved drug labels (2000–2020). J Pers Med 2021; 11(3): 179.
[http://dx.doi.org/10.3390/jpm11030179] [PMID: 33806453]
[18]
Bethune G, Bethune D, Ridgway N, Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J Thorac Dis 2010; 2(1): 48-51.
[PMID: 22263017]
[19]
Reardon DA, Wen PY, Mellinghoff IK. Targeted molecular therapies against epidermal growth factor receptors: Past experiences and challenges. Neuro Oncol 2014; 16(S8): viii7-viii13.
[http://dx.doi.org/10.1093/neuonc/nou232]
[20]
Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT. Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat 2012; 136(2): 331-45.
[http://dx.doi.org/10.1007/s10549-012-2289-9 ] [PMID: 23073759]
[21]
Eitsuka T, Tatewaki N, Nishida H, Nakagawa K, Miyazawa T. Synergistic anticancer effect of tocotrienol combined with chemotherapeutic agents or dietary components: A review. Int J Mol Sci 2016; 17(10): 1605.
[http://dx.doi.org/10.3390/ijms17101605] [PMID: 27669218]
[22]
Ardito F, Giuliani M, Perrone D, Troiano G, Muzio LL. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med 2017; 40(2): 271-80.
[http://dx.doi.org/10.3892/ijmm.2017.3036] [PMID: 28656226]
[23]
Bacchi CE, Ciol H, Queiroga EM, Benine LC, Silva LH, Ojopi EB. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. Clinics 2012; 67(5): 419-24.
[http://dx.doi.org/10.6061/clinics/2012(05)03 ] [PMID: 22666783]
[24]
Ferrer I, Zugazagoitia J, Herbertz S, John W, Ares PL, Bindert SG. KRAS-Mutant non-small cell lung cancer: From biology to therapy. Lung Cancer 2018; 124: 53-64.
[http://dx.doi.org/10.1016/j.lungcan.2018.07.013 ] [PMID: 30268480]
[25]
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications. Mol Biol Int 2014; 2014: 852748.
[26]
Foster B, Zaidi D, Young T, Mobley M, Kerr B. CD117/c-kit in cancer stem cell-mediated progression and therapeutic resistance. Biomedicines 2018; 6(1): 31.
[http://dx.doi.org/10.3390/biomedicines6010031 ] [PMID: 29518044]
[27]
Liang J, Wu YL, Chen BJ, Zhang W, Tanaka Y, Sugiyama H. The C-kit receptor-mediated signal transduction and tumor-related diseases. Int J Biol Sci 2013; 9(5): 435-43.
[http://dx.doi.org/10.7150/ijbs.6087] [PMID: 23678293]
[28]
Magid AAF. The potential of c-KIT kinase inhibitors in cancer treatment. ACS Med Chem Lett 2021; 12(8): 1191-2.
[http://dx.doi.org/10.1021/acsmedchemlett.1c00332 ] [PMID: 34413937]
[29]
De Las Rivas J, Brozovic A, Izraely S, Pais CA, Witz IP, Figueroa A. Cancer drug resistance induced by EMT: Novel therapeutic strategies. Arch Toxicol 2021; 95(7): 2279-97.
[http://dx.doi.org/10.1007/s00204-021-03063-7 ] [PMID: 34003341]
[30]
Pottier C, Fresnais M, Gilon M, Jérusalem G, Longuespée R, Sounni NE. Tyrosine kinase inhibitors in cancer: breakthrough and challenges of targeted therapy. Cancers 2020; 12(3): 731.
[http://dx.doi.org/10.3390/cancers12030731 ] [PMID: 32244867]
[31]
Gasch C, Ffrench B, O’Leary JJ, Gallagher MF. Catching moving targets: Cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention. Mol Cancer 2017; 16(1): 43.
[http://dx.doi.org/10.1186/s12943-017-0601-3 ] [PMID: 28228161]
[32]
Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci 2019; 234: 116781.
[http://dx.doi.org/10.1016/j.lfs.2019.116781 ] [PMID: 31430455]
[33]
Yu HA, Sima CS, Huang J, et al. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2013; 8(3): 346-51.
[http://dx.doi.org/10.1097/JTO.0b013e31827e1f83 ] [PMID: 23407558]
[34]
Berg M, Soreide K. EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways in colorectal cancer: Implications for targeted therapy. Discov Med 2012; 14(76): 207-14.
[PMID: 23021375]
[35]
Chan CWH, Law BMH, So WKW, Chow KM, Waye MMY. Pharmacogenomics of breast cancer: Highlighting CYP2D6 and tamoxifen. J Cancer Res Clin Oncol 2020; 146(6): 1395-404.
[http://dx.doi.org/10.1007/s00432-020-03206-w ] [PMID: 32270286]
[36]
Yang B, Wang JQ, Tan Y, Yuan R, Chen ZS, Zou C. RNA methylation and cancer treatment. Pharmacol Res 2021; 174: 105937.
[http://dx.doi.org/10.1016/j.phrs.2021.105937 ] [PMID: 34648969]
[37]
Xia H, Ooi LLPJ, Hui KM. MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology 2013; 58(2): 629-41.
[http://dx.doi.org/10.1002/hep.26369] [PMID: 23471579]
[38]
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther 2016; 1(1): 15004.
[http://dx.doi.org/10.1038/sigtrans.2015.4] [PMID: 29263891]
[39]
Yao Q, Chen Y, Zhou X. The roles of microRNAs in epigenetic regulation. Curr Opin Chem Biol 2019; 51: 11-7.
[http://dx.doi.org/10.1016/j.cbpa.2019.01.024 ] [PMID: 30825741]
[40]
Chowdhury PS, Chamoto K, Honjo T. Combination therapy strategies for improving PD‐1 blockade efficacy: A new era in cancer immunotherapy. J Intern Med 2018; 283(2): 110-20.
[http://dx.doi.org/10.1111/joim.12708] [PMID: 29071761]
[41]
Taylor MH, Lee CH, Makker V, et al. Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumours. J Clin Oncol 2020; 38(11): 1154-63.
[http://dx.doi.org/10.1200/JCO.19.01598] [PMID: 31961766]
[42]
Chau V, Bilusic M. Pembrolizumab in combination with axitinib as first-line treatment for patients with renal cell carcinoma (RCC): Evidence to date. Cancer Manag Res 2020; 12: 7321-30.
[http://dx.doi.org/10.2147/CMAR.S216605 ] [PMID: 32884346]
[43]
Mollica V, Nunno DV, Massari F. Pembrolizumab plus axitinib: A new treatment option for patients with metastatic renal cell carcinoma. Chin Clin Oncol 2019; 8(S1): S21.
[http://dx.doi.org/10.21037/cco.2019.04.05 ] [PMID: 31280574]
[44]
Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 2021; 384(14): 1289-300.
[http://dx.doi.org/10.1056/NEJMoa2035716 ] [PMID: 33616314]
[45]
Ahmed S, Zhou Z, Zhou J, Chen SQ. Pharmacogenomics of drug metabolising enzymes and transporters: Relevance to precision medicine. Genomics Proteom Bioinform 2016; 14(5): 298-313.
[http://dx.doi.org/10.1016/j.gpb.2016.03.008 ] [PMID: 27729266]
[46]
Michels J, Vitale I, Saparbaev M, Castedo M, Kroemer G. Predictive biomarkers for cancer therapy with PARP inhibitors. Oncogene 2014; 33(30): 3894-907.
[http://dx.doi.org/10.1038/onc.2013.352] [PMID: 24037533]
[47]
Tarantino P, Trapani D, Morganti S, et al. Opportunities and challenges of implementing Pharmacogenomics in cancer drug development. Cancer Drug Resist 2019; 2(1): 43-52.
[http://dx.doi.org/10.20517/cdr.2018.22]
[48]
Nave Op, Elbaz M, Mendrazitsky BS. Analysis of a breast cancer mathematical model by a new method to find an optimal protocol for HER-2 positive cancer. Biosystems 2020; 197: 104191.
[http://dx.doi.org/10.1016/j.biosystems.2020.104191]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy