REVOLUTIONIZING DRUG DISCOVERY: UTILIZING BIOMARKERS FOR PRECISION MEDICINE AND TARGETED THERAPIES
DOI:
https://doi.org/10.22159/ajpcr.2024v17i7.51039Keywords:
Drug discovery, Biomarkers, Cancer, COVID 19,, Applications, TypesAbstract
Drug discovery remains a complex and time-consuming process, often hindered by inefficiencies and high failure rates. Biomarkers, measurable indicators of biological processes, have emerged as powerful tools to revolutionize this landscape. This article explores the multifaceted role of biomarkers throughout the drug discovery, from target identification and drug development to clinical trials and patient stratification. We highlight how biomarkers enhance our understanding of disease mechanisms, facilitate the selection of promising drug candidates, and enable objective assessment of drug efficacy and safety. Furthermore, the integration of biomarkers with companion diagnostics allows for personalized medicine approaches, tailoring treatment options to individual patient needs. We discuss the various types of biomarkers employed in drug discovery, including genomic, proteomic, and imaging biomarkers, while acknowledging the challenges associated with their validation and regulatory approval. In conclusion, the strategic utilization of biomarkers holds immense potential to streamline drug discovery, accelerate development timelines, and ultimately bring safer and more effective therapies to patients.
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Mayeux R. Biomarkers: Potential uses and limitations. NeuroRX. 2004 Apr;1(2):182-8. doi: 10.1602/neurorx.1.2.182
Zhou W, Wang Y, Gu X, Feng Z, Lee K, Peng Y, et al. Importance of general adiposity, visceral adiposity and vital signs in predicting blood biomarkers using machine learning. Int J Clin Pract. 2020;75(1):e13664. doi: 10.1111/ijcp.13664
Siddiqui I, Majid H, Abid S. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases. World J Gastrointest Pharmacol Ther. 2017;8(1):39-46. doi: 10.4292/wjgpt.v8.i1.39
Van Assche G. Fecal biomarkers for the diagnosis and management of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011 Jun;7(6):396-8. PMID: 21869871, PMCID: PMC3151412
Colvin OC, Kransdorf MJ, Roberts CC, Chivers FS, Lorans R, Beauchamp CP, et al. Leukocyte esterase analysis in the diagnosis of joint infection: Can we make a diagnosis using a simple urine dipstick? Skeletal Radiol. 2015 Jan 29;44(5):673-7. doi: 10.1007/s00256-015- 2097-5
Ang SH, Thevarajah M, Alias Y, Khor SM. Current aspects in hemoglobin A1c detection: A review. Clin Chim Acta. 2015 Jan;439:202-11. doi: 10.1016/j.cca.2014.10.019
Sinha N, Mishra TK, Singh T, Gupta N. Effect of iron deficiency anemia on hemoglobin A1c levels. Ann Lab Med. 2012 Jan 1;32(1):17-22. doi: 10.3343/alm.2012.32.1.17
Naylor S. Biomarkers: Current perspectives and future prospects. Expert Rev Mol Diagn. 2003 Sep;3(5):525-9. doi: 10.1586/14737159.3.5.525
Vasan RS. Biomarkers of cardiovascular disease: Molecular basis and practical considerations. Circulation. 2006 May 16;113(19):2335-62. doi: 10.1161/circulationaha.104.482570
Osumi H, Shinozaki E, Yamaguchi K. Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer. Cancers (Basel). 2020 Jun 13;12(6):1566. doi: 10.3390/ cancers12061566
Katz R. Biomarkers and surrogate markers: An FDA perspective. NeuroRX. 2004 Apr;1(2):189-95. doi: 10.1602/neurorx.1.2.189
Meigs JB. Multiple biomarker prediction of type 2 diabetes. Diabetes Care. 2009 Jul 1;32(7):1346-8. doi: 10.2337/dc09-0754
Trusheim MR, Burgess B, Hu SX, Long T, Averbuch SD, Flynn AA, et al. Quantifying factors for the success of stratified medicine. Nat Rev Drug Discov. 2011 Oct 31;10(11):817-33. doi: 10.1038/nrd3557
Fernando JJ, Biswas R, Biswas L. Non‐invasive molecular biomarkers for monitoring solid organ transplantation: A comprehensive overview. Int J Immunogenet. 2024 Jan 10;51(2):47-62. doi: 10.1111/iji.12654
Deore AB, Dhumane JR, Wagh R, Sonawane R. The stages of drug discovery and development process. Asian J Pharm Res Dev. 2019 Dec 15;7(6):62-7. doi: 10.22270/ajprd.v7i6.616
Freidlin B, McShane LM, Korn EL. Randomized clinical trials with biomarkers: Design issues. J Natl Cancer Inst. 2010 Jan 14;102(3):152-60. doi: 10.1093/jnci/djp477
Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov. 2003 Jul;2(7):566-80. doi: 10.1038/nrd1130
Zhang X, Jonassen I, Goksøyr A. Machine Learning Approaches for Biomarker Discovery Using Gene Expression Data. Brisbane: Exon Publications; 2021. Available from: https://www.ncbi.nlm. nih.gov/books/NBK569564/ doi: 10.36255/exonpublications. bioinformatics.2021.ch4
Hale JE, Butler JP, Gelfanova V, You JS, Knierman MD. A simplified procedure for the reduction and alkylation of cysteine residues in proteins prior to proteolytic digestion and mass spectral analysis. Anal Biochem. 2004 Oct;333(1):174-81. doi: 10.1016/j.ab.2004.04.013
Diamandis EP. Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: Opportunities and potential limitations. Mol Cell Proteomics. 2004 Jan 29; 3(4):367-78. doi: 10.1074/mcp.r400005- mcp200
Kam RK, Poon TC. The Potentials of glycomics in biomarker discovery. Clin Proteom. 2008 Sep 4;4(3-4):67-79. doi: 10.1007/s12014-008- 9017-9
Hu C, van der Heijden R, Wang M, van der Greef J, Hankemeier T, Xu G. Analytical strategies in lipidomics and applications in disease biomarker discovery. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep;877(26):2836-46. doi: 10.1016/j.jchromb.2009.01.03823. Emwas AH, Luchinat C, Turano P, Tenori L, Roy R, Salek RM, et al. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: A review. Metabolomics. 2014 Nov 21;11(4):872-94. doi: 10.1007/ s11306-014-0746-7
Kumar S, Mohan A, Guleria R. Biomarkers in cancer screening, research and detection: Present and future: A review. Biomarkers. 2006 Jan;11(5):385-405. doi: 10.1080/13547500600775011
Scherf U, Becker R, Chan M, Hojvat S. Approval of novel biomarkers: FDA’s perspective and major requests. Scand J Clin Lab Invest Suppl. 2010 Jan;242:96-102. doi: 10.3109/00365513.2010.493415
Zhou Q, Andersson R, Hu D, Bauden M, Kristl T, Sasor A, et al. Quantitative proteomics identifies brain acid soluble protein 1 (BASP1) as a prognostic biomarker candidate in pancreatic cancer tissue. EBioMedicine. 2019 May;43:282-94. doi: 10.1016/j. ebiom.2019.04.008
Ortega-Romero M, Rojas-Lima E, Rubio-Gutiérrez JC, Aztatzi- Aguilar OG, Narváez-Morales J, Esparza-García M, et al. Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population. Biometals. 2024 Apr 20;37(3):721-37. doi: 10.1007/s10534-024-00603-3
Wishart DS, Bartok B, Oler E, Liang KY, Budinski Z, Berjanskii M, et al. An online database of molecular biomarkers. Nucleic Acids Res. 2020 Nov 27;49(D1):D1259-67. doi: 10.1093/nar/gkaa1067
Cardiff RD, Gregg JP, Miller JW, Axelrod DE, Borowsky AD. Histopathology as a Predictive Biomarker: Strengths and Limitations. J Nutr. 2006 Oct;136(10):2673S-5. doi: 10.1093/jn/136.10.2673s
Endl E, Gerdes J. The Ki-67 protein: Fascinating forms and an unknown function. Exp Cell Res. 2000 Jun;257(2):231-7. doi: 10.1006/ excr.2000.4888
Raphael MJ, Chan DL, Law C, Singh S. Principles of diagnosis and management of neuroendocrine tumours. CMAJ. 2017 Mar 12;189(10):E398-404. doi: 10.1503/cmaj.160771
Lindboe CF, Torp SH. Comparison of Ki-67 equivalent antibodies. J Clin Pathol. 2002 Jun 1;55(6):467-71. doi: 10.1136/jcp.55.6.467
Viale G, Hanlon Newell AE, Walker E, Harlow G, Bai I, Russo L, et al. Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes. Breast Cancer Res Treat. 2019 Aug 17;178(2):451-8. doi: 10.1007/s10549-019-05402-w
Feeley LP, Mulligan AM, Pinnaduwage D, Bull SB, Andrulis IL. Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information. Mod Pathol. 2014 Apr;27(4):554-61. doi: 10.1038/modpathol.2013.153
Stark JR, Perner S, Stampfer MJ, Sinnott JA, Finn S, Eisenstein AS, et al. Gleason score and lethal prostate cancer: Does 3 + 4 = 4 + 3? J Clin Oncol. 2009 Jul 20;27(21):3459-64. doi: 10.1200/jco.2008.20.4669
Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, et al. A contemporary prostate cancer grading system: A validated alternative to the gleason score. Eur Urol. 2016 Mar;69(3):428-35. doi: 10.1016/j.eururo.2015.06.046
Harry VN. Novel imaging techniques as response biomarkers in cervical cancer. Gynecol Oncol. 2010 Feb;116(2):253-61. doi: 10.1016/j. ygyno.2009.11.003
Berger M, Yang Q, Maier A. X-ray imaging. In: Medical Imaging Systems: An Introductory Guide. Cham: Springer; 2018.
Katti G, Ara SA, Shireen A. Magnetic resonance imaging (MRI) - A review. Int J Dent Clin. 2011;3(1):65-70.
Patel PR, De Jesus O. CT Scan. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih. gov/books/NBK567796 [Last accessed on 2023 Jan 02].
Ferrer R, Artigas A. Physiologic parameters as biomarkers: What can we learn from physiologic variables and variation? Crit Care Clin. 2011 Apr;27(2):229-40. doi: 10.1016/j.ccc.2010.12.008
Sicari R, Cortigiani L. The clinical use of stress echocardiography in ischemic heart disease. Cardiovasc Ultrasound. 2017 Mar 21;15(1):7. doi: 10.1186/s12947-017-0099-2
Śledzińska P, Bebyn MG, Furtak J, Kowalewski J, Lewandowska MA. Prognostic and predictive biomarkers in gliomas. Int J Mol Sci. 2021 Sep 26;22(19):10373. doi: 10.3390/ijms221910373
Jørgensen JT. Predictive biomarkers and clinical evidence. Basic Clin Pharmacol Toxicol. 2021 Mar 13;128(5):642-8. doi: 10.1111/ bcpt.13578
Tian X, Wei F, Wang L, Yu W, Zhang N, Zhang X, et al. Herceptin enhances the antitumor effect of natural killer cells on breast cancer cells expressing human epidermal growth factor receptor-2. Front Immunol. 2017 Oct 30;8:1426. doi: 10.3389/fimmu.2017.01426
De Cuyper A, Van Den Eynde M, Machiels JP. HER2 as a predictive biomarker and treatment target in colorectal cancer. Clin Colorectal Cancer. 2020 Jun;19(2):65-72. doi: 10.1016/j.clcc.2020.02.007
Rimawi MF, Schiff R, Osborne CK. Targeting HER2 for the treatment of breast cancer. Annu Rev Med. 2015 Jan 14;66(1):111-28. doi: 10.1146/ annurev-med-042513-015127
Sitia L, Sevieri M, Signati L, Bonizzi A, Chesi A, Mainini F, et al. HER-2-targeted nanoparticles for breast cancer diagnosis and treatment. Cancers (Basel). 2022 May 13;14(10):2424. doi: 10.3390/ cancers14102424
Vakiani E, Solit DB. KRAS and BRAF: Drug targets and predictive biomarkers. J Pathol. 2010 Oct 28;223(2):220-30. doi: 10.1002/ path.2796
Nalejska E, Mączyńska E, Lewandowska MA. Prognostic and predictive biomarkers: Tools in personalized oncology. Mol Diagn Ther. 2014 Jan 3;18(3):273-84. doi: 10.1007/s40291-013-0077-9
Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: Prediction, detection and monitoring. Nat Rev Cancer. 2008 Apr;8(4):268-78. doi: 10.1038/nrc2351
Merriel SW, Funston G, Hamilton W. Prostate cancer in primary care. Adv Ther. 2018 Aug 10;35(9):1285-94. doi: 10.1007/s12325-018- 0766-1
Vaidya SR, Aeddula NR. Chronic kidney disease. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535404 [Last accessed on 2022 Oct 24].
Madu CO, Lu Y. Novel diagnostic biomarkers for prostate cancer. J Cancer. 2010;1:150-77. doi: 10.7150/jca.1.150
Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR. CA125 and ovarian cancer: A comprehensive review. Cancers (Basel). 2020 Dec 11;12(12):3730. doi: 10.3390/cancers12123730
Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res. 2019 Mar 27;12(1):28. doi: 10.1186/s13048-019-0503-7
Pandian R, Cole LA, Palomaki GE. Second-trimester maternal serum invasive trophoblast antigen: A marker for down syndrome screening. Clin Chem. 2004 Aug 1;50(8):1433-5. doi: 10.1373/ clinchem.2004.032839
Colburn WA. Biomarkers in drug discovery and development: From target identification through drug marketing. J Clin Pharmacol. 2003 Apr;43(4):329-41. doi: 10.1177/0091270003252480
Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm Sin B. 2022 Jul;12(7):3049-62. doi: 10.1016/j.apsb.2022.02.002
Schuck RN, Delfino JG, Leptak C, Wagner JA. Biomarkers in drug development. In: Atkinson’s Principles of Clinical Pharmacology. Amsterdam: Elsevier; 2022. p. 323-42. doi: 10.1016/b978-0-12- 819869-8.00029-x
Masuda T, Mori A, Ito S, Ohtsuki S. Quantitative and targeted proteomics-based identification and validation of drug efficacy biomarkers. Drug Metab Pharmacokinet. 2021 Feb;36:100361. doi: 10.1016/j.dmpk.2020.09.006
Zhao X, Modur V, Carayannopoulos LN, Laterza OF. Biomarkers in pharmaceutical research. Clin Chem. 2015 Nov 1;61(11):1343-53. doi: 10.1373/clinchem.2014.231712
Buyse M, Michiels S, Sargent DJ, Grothey A, Matheson A, de Gramont A. Integrating biomarkers in clinical trials. Expert Rev Mol Diagn. 2011 Mar;11(2):171-82. doi: 10.1586/erm.10.120
Saigusa D, Matsukawa N, Hishinuma E, Koshiba S. Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics. Drug Metab Pharmacokinet. 2021 Apr;37:100373. doi: 10.1016/j.dmpk.2020.11.008
Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011 Jun 7;8(8):467-77. doi: 10.1038/nrclinonc.2011.76
Satish BN, Srikala P, Maharudrappa B, Awanti SM, Kumar P, Hugar D. Saliva: A tool in assessing glucose levels in Diabetes Mellitus. J Int Oral Health. 2014 Apr;6(2):114-7. PMID: 24876711, PMC4037799
Kramer JA, Sagartz JE, Morris DL. The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates. Nat Rev Drug Discov. 2007 Aug;6(8):636-49. doi: 10.1038/nrd2378
Narayan V, Thompson EW, Demissei B, Ho JE, Januzzi JL Jr., Ky B. Mechanistic Biomarkers informative of both cancer and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol. 2020 Jun;75(21):2726-37. doi: 10.1016/j.jacc.2020.03.06769. Sanajou S, Şahin G. Mechanistic biomarkers in toxicology. Turk J Pharm Sci. 2021 Jun 18;18(3):376-84. doi: 10.4274/tjps.galenos.2020.10270
Colburn WA, Lee JW. Biomarkers, validation and pharmacokinetic-pharmacodynamic modelling. Clin Pharmacokinet. 2003;42(12):997- 1022. doi: 10.2165/00003088-200342120-00001
Eddershaw PJ, Beresford AP, Bayliss MK. ADME/PK as part of a rational approach to drug discovery. Drug Discov Today. 2000 Sep;5(9):409-14. doi: 10.1016/s1359-6446(00)01540-3
Oellerich M, Barten MJ, Armstrong VW. Biomarkers: The link between therapeutic drug monitoring and pharmacodynamics. Ther Drug Monit. 2006 Feb;28(1):35-8. doi: 10.1097/01.ftd.0000194503.85763.f5
Gunderson BW, Ross GH, Ibrahim KH, Rotschafer JC. What do we really know about antibiotic pharmacodynamics? Pharmacotherapy. 2001 Nov;21(11 Pt 2):302S-18. doi: 10.1592/phco.21.18.302s.33905
Pogribny IP. MicroRNAs as biomarkers for clinical studies. Exp Biol Med (Maywood). 2017 Sep 15;243(3):283-90. doi: 10.1177/1535370217731291
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: Role of inflammation triggers and cytokines. Front Immunol. 2018 Apr 9;9:586. doi: 10.3389/ fimmu.2018.00586
Davis KD, Aghaeepour N, Ahn AH, Angst MS, Borsook D, Brenton A, et al. Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities. Nat Rev Neurol. 2020 Jun 15;16(7):381-400. doi: 10.1038/s41582-020- 0362-2
Schomaker S, Ramaiah S, Khan N, Burkhardt J. Safety biomarker applications in drug development. J Toxicol Sci. 2019;44(4):225-35. doi: 10.2131/jts.44.225
Battula S. Challenges and opportunities to overcome the threat of antimicrobial resistance in public health. Microbiol Int J. 2021;3(1):113. doi: 10.37532/tsmy.2021.3(1).113
Samprathi M, Jayashree M. Biomarkers in COVID-19: An up-to-date review. Front Pediatr. 2021 Mar 30;8:607647. doi: 10.3389/ fped.2020.607647
Cheng L, Yang JZ, Bai WH, Li ZY, Sun LF, Yan JJ, et al. Prognostic value of serum amyloid A in patients with COVID-19. Infection. 2020 Jul 30;48(5):715-22. doi: 10.1007/s15010-020-01468-7
Wang L. C-reactive protein levels in the early stage of COVID-19. Méd Mal Infect. 2020 Jun;50(4):332-4. doi: 10.1016/j.medmal.2020.03.007
Urieli-Shoval S, Linke RP, Matzner Y. Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states. Curr Opin Hematol. 2000 Jan;7(1):64-9. doi: 10.1097/00062752- 200001000-00012
Li H, Xiang X, Ren H, Xu L, Zhao L, Chen X, et al. Serum Amyloid A is a biomarker of severe coronavirus disease and poor prognosis. J Infect. 2020 Jun;80(6):646-55. doi: 10.1016/j.jinf.2020.03.035
Ali N. Elevated level of C‐reactive protein may be an early marker to predict risk for severity of COVID‐19. J Med Virol. 2020 Jun 9;92(11):2409-11. doi: 10.1002/jmv.26097
Sabetian G, Feiz F, Shakibafard A, Fard HA, Sefidbakht S, Jafari SH, et al. Challenges of diagnosis of COVID-19 in trauma patients: A case series. Trauma. 2020 Aug 17;23(3):218-29. doi: 10.1177/1460408620950602
Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19 - A systematic review. Life Sci. 2020 Aug;254:117788. doi: 10.1016/j.lfs.2020.117788
Kamel HF, Al-Amodi HS. Cancer biomarkers. In: Role of Biomarkers in Medicine. London: IntechOpen; 2016. doi: 10.5772/62421
Ullah MF, Aatif M. The footprints of cancer development: Cancer biomarkers. Cancer Treat Rev. 2009 May;35(3):193-200. doi: 10.1016/j. ctrv.2008.10.004
Allin KH, Bojesen SE, Nordestgaard BG. Inflammatory biomarkers and risk of cancer in 84,000 individuals from the general population. Int J Cancer. 2016 Jun;139(7):1493-500. doi: 10.1002/ijc.30194
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002 Jun;417(6892):949-54. doi: 10.1038/nature00766
Brzeziańska E, Pastuszak-Lewandoska D, Wojciechowska K, Migdalska-Sek M, Cyniak-Magierska A, Nawrot E, et al. Investigation of V600E BRAF mutation in papillary thyroid carcinoma in the Polish population. Neuro Endocrinol Lett. 2007;28:351-9.
Mishra A, Verma M. Cancer biomarkers: Are we ready for the prime time? Cancers (Basel). 2010 Mar 22;2(1):190-208. doi: 10.3390/ cancers2010190
Alao JP. The regulation of cyclin D1 degradation: Roles in cancer development and the potential for therapeutic invention. Mol Cancer. 2007;6(1):24. doi: 10.1186/1476-4598-6-24
Joo M, Kang YK, Kim M, Lee HK, Jang J. Cyclin D1 overexpression in hepatocellular carcinoma. Liver. 2001 Apr;21(2):89-95. doi: 10.1034/j.1600-0676.2001.021002089.x
Selvaggi G, Novello S, Torri V, Leonardo E, De Giuli P, Borasio P, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol. 2004 Jan;15(1):28-32. doi: 10.1093/annonc/mdh011
Bohanes P, LaBonte MJ, Lenz H-J. A review of excision repair cross-complementation group 1 in colorectal cancer. Clin Colorectal Cancer. 2011 Sep;10(3):157-64. doi: 10.1016/j.clcc.2011.03.024
Scharer OD. Nucleotide excision repair in eukaryotes. Cold Spring Harb Perspect Biol. 2013 Oct 1;5(10):a012609. doi: 10.1101/cshperspect.a012609
Patel MR, Zhao N, Ang M, Stadler ME, Fritchie K, Weissler MC, et al. ERCC1 protein expression is associated with differential survival in oropharyngeal head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 2013 Jul 11;149(4):587-95. doi: 10.1177/0194599813496522
Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004 Jun;59(2):S21-6. doi: 10.1016/j. ijrobp.2003.11.041
Masood A, Kancha RK, Subramanian J. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer harboring uncommon EGFR mutations: Focus on afatinib. Semin Oncol. 2019 Jun;46(3):271-83. doi: 10.1053/j.seminoncol.2019.08.004
Giaccone G, Rodriguez JA. EGFR inhibitors: What have we learned from the treatment of lung cancer? Nat Clin Pract Oncol. 2005 Nov;2(11):554-61. doi: 10.1038/ncponc0341
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