Keywords
kişiselleştirilmiş tıp
dijital ikiz
derin öğrenme
nanomedisin
How to Cite
Abstract
Kolorektal kanser, uzun süre asemptomatik seyredebilmesi nedeniyle çoğu zaman ileri evrede teşhis edilen ve mortalite riski yüksek bir sağlık problemidir. Bu çalışma, yazılım mühendisliği, yapay zekâ, nanoteknoloji ve biyoinformatik yaklaşımları bütünleştirerek erken evrede tespit ve hedefli tedaviye yönelik dört katmanlı bir “Akıllı İlaç Sistemi” önermektedir. Önerilen sistem, bağırsak içinde gerçek zamanlı görüntüleme ve derin öğrenme tabanlı analiz ile tümöral dokunun tespitini sağlayan bir algılama katmanı, sıvı biyopsi ve genomik veriler aracılığıyla nano-kapsül hedeflerinin dinamik olarak güncellendiği bir uyarlama (rolling update) mekanizması, yalnızca belirli biyokimyasal koşulların (pH düşüklüğü, enzim ekspresyonu ve hedef protein varlığı gibi) birlikte sağlanması durumunda ilaç salımını aktive eden mantıksal bir kontrol (AND kapısı) yapısı ve tüm tedavi sürecini gerçek zamanlı olarak izlenebilir ve yönetilebilir hale getiren dijital ikiz platformundan oluşmaktadır. Bu katmanlı mimari hem hedef dışı toksisiteyi azaltmayı hem de tümörün adaptif direnç mekanizmalarını sınırlamayı amaçlamaktadır. Sistem, kişiselleştirilmiş, programlanabilir ve veri güdümlü tedavi yaklaşımıyla modern onkoloji için bütüncül bir kavramsal çerçeve sunmaktadır.
References
[1] Hudson, A. (2026). A silent shift: Rising early-onset colorectal cancer rates. LMH Health. https://www.lmh.org/news/2026-news/a-silent-shift-rising-early-onset-colorectal-cancer-rates/
[2] Markopoulos, C. K., ve ark. (2024). Colorectal cancer: Current updates and future perspectives. Cancers. https://pmc.ncbi.nlm.nih.gov/articles/PMC10780254/
[3] Cai, D., ve ark. (2024). A new strategy for immunotherapy of MSS-type advanced colorectal cancer: Multi-pathway combination therapy with PD-1/PD-L1 inhibitors. Immunology, 173(2), 209-226. https://doi.org/10.1111/imm.13785
[4] American Cancer Society. (2023-2024). Detecting colorectal cancer / Facts & figures 2023-2025. https://www.cancer.org/cancer/types/colon-rectal-cancer/detection-diagnosis-staging/detection.html
[5] Nikumbh, T., ve ark. (2024). National trends in the incidence of sporadic malignant colorectal polyps in young patients (20-49 years): An 18-year SEER database analysis. Medicina, 60(4), 673. https://doi.org/10.3390/medicina60040673
[6] Wang, X., ve ark. (2025). Harnessing gut microbiota for colorectal cancer therapy: From clinical insights to therapeutic innovations. npj Biofilms and Microbiomes. https://www.nature.com/articles/s41522-025-00818-3
[7] Sultany, A., Chikatimalla, R., & Rao, A., ve ark. (2025). Real-time artificial intelligence versus standard colonoscopy in the early detection of colorectal cancer: A systematic review and meta-analysis. Healthcare, 13(19), 2517. https://doi.org/10.3390/healthcare13192517
[8] Rachamala, H. K. (2025). Translational advances in lipid nanoparticle drug delivery systems for cancer therapy: Current status and future horizons. Pharmaceutics, 17(10), 1315. https://doi.org/10.3390/pharmaceutics17101315
[9] Mahmoudian, F., ve ark. (2024). Aptamers as an approach to targeted cancer therapy. Cancer Cell International, 24, 108. https://doi.org/10.1186/s12935-024-03295-4
[10] Hasan, M., Evett, C. G., & Burton, J. (2024). Advances in nanoparticle-based targeted drug delivery systems for colorectal cancer therapy: A review. arXiv. https://arxiv.org/pdf/2409.05222
[11] Ye, S., Chen, S., Basava, V., ve ark. (2026). AND logic nanoparticle for precision immunotherapy of metastatic cancers. Nature Nanotechnology. https://doi.org/10.1038/s41565-026-02130-3
[12] Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors, 18(10), 3249. https://doi.org/10.3390/s18103249
[13] Li, X., & Xu, Z. (2025). Applications of matrix metalloproteinase-9-related nanomedicines in tumors and vascular diseases. Pharmaceutics, 17(4), 479. https://www.mdpi.com/1999-4923/17/4/479
[14] Guo, H., ve ark. (2024). Stimuli-responsive aptamer-drug conjugates for targeted drug delivery and controlled drug release. Advanced Healthcare Materials, 13, 2401020. https://doi.org/10.1002/adhm.202401020
[15] Mohammadi, ve ark. (2024). Progressive cancer targeting by programmable aptamer-tethered nanostructures. MedComm, 5, e775. https://doi.org/10.1002/mco2.775
[16] Silva, A., & Vale, N. (2025). Digital twins in personalized medicine: Bridging innovation and clinical reality. Journal of Personalized Medicine, 15(11), 503. https://doi.org/10.3390/jpm15110503
[17] Maharjan, R., Kim, N. A., Kim, K. H., & Jeong, S. H. (2025). Transformative roles of digital twins from drug discovery to continuous manufacturing. International Journal of Pharmaceutics: X, 10, 100409. https://pmc.ncbi.nlm.nih.gov/articles/PMC12516570/
[18] Elmas, E. T. (2020). ELMAS’s theory of thermodynamics: A scientific approach for 5th law of thermodynamics - A theoretical application example for medical thermodynamics. Open Access Journal of Biogeneric Science and Research, 2(1). https://doi.org/10.46718/JBGSR.2020.01.000030
[19] Elmas, E. T. (2024). Medical treatment method of Alzheimer’s disease & Parkinson’s disease by the help of the natural musical sound of Nay-i Serif. International Journal of Clinical Medicine Case Reports, 42(3), 004. https://doi.org/10.46998/IJCMCR.2024.42.001039
[20] Elmas, E. T. (2020). Medical treatment method of bio-robotic resonance and thermodynamical interaction with analogy of frequency-resonance setting formation. Open Access Journal of Biogeneric Science and Research, 1(1). https://doi.org/10.46718/JBGSR.2020.01.000007
[21] Elmas, E. T. (2020). Scope of applications for medical technique at science and engineering. Open Access Journal of Biogeneric Science and Research, 1(1). https://doi.org/10.46718/JBGSR.2020.01.000002
[22] Elmas, E. T. (2024). System design and development of a novel unique neuro-physical medical treatment method for SMA-spinal muscular atrophy disease and for similar neurological muscle diseases. Herculean Research, 4(1), 90-97.
[23] Das, F., Elmas, E. T., & Bucak, I. O. (2024). Innovative use of machine learning-aided virtual reality and natural language processing technologies in dyslexia diagnosis and treatment phases. In Digital frontiers - Healthcare, education, and society in the metaverse era. IntechOpen. https://doi.org/10.5772/intechopen.1006621
[24] Elmas, E. T. (2024). Design of bionic eye and artificial vision system; a unique project Mobile Bio-Eye-Tronic System. Herculean Research, 4(1), 97-100. https://dx.doi.org/10.70222/hres23
[25] Elmas, E. T. (2024). Project for amphibious mobile snow track ambulance for healthcare system. American Journal of Biomedical Science & Research, 22(4). https://doi.org/10.34297/AJBSR.2024.22.002990
[26] Elmas, E. T., & Bucak, I. O. (2023). Modeling and simulation of smart-drug algorithms through frequency modulation for the treatment of Covid-19 and similar viruses. Global Journal of Research in Medical Sciences, 3(5), 1-6. https://doi.org/10.5281/zenodo.10051793
[27] Elmas, E. T., & Bucak, I. O. (2024). FM modulated smart drug algorithm for the treatment of cancer cells. Global Journal of Research in Medical Sciences, 4(1), 1-6. https://doi.org/10.5281/zenodo.10463529
[28] Elmas, E. T. (2023). Prototype design, production and functioning of a portable (movable), home-type hemodialysis machine (unit). Global Journal of Research in Medical Sciences, 3(6), 11-12. https://doi.org/10.5281/zenodo.10252972
[29] Elmas, E. T. (2019). Thermodynamical balance associated with energy transfer analysis of the universe space as a pressure vessel analogy. Journal of Applied Sciences, 2019(1).
[30] Elmas, E. T. (2017). Prospective characteristics of contemporary engineer: Contribution and role of the mechanical engineer to the organization management and productivity. In C. Machado & J. P. Davim (Eds.), Productivity and organizational management (Chapter 7). De Gruyter. https://doi.org/10.1515/9783110355796-007
[31] Elmas, E. T. (2017). Prospective characteristics of contemporary engineer: Contribution and role of the mechanical engineer to the organization management and productivity. De Gruyter. https://doi.org/10.1515/9783110355796-007
[32] Elmas, E. T. (2024). Design of bio-artificial liver organ. Journal of Biomedical Sciences and Biotechnology Research, 2(3), 1-4. https://doi.org/10.61440/JBSBR.2024.v2.12
[33] Elmas, E. T. (2024). Design of bionic ear-cochlear implant and artificial hearing system; a unique project Mobile Bio-Ear-Tronic System. Global Journal of Research in Medical Sciences, 4(2). https://doi.org/10.5281/zenodo.12751385
[34] Elmas, E. T. (2014). Cagimizin muhendisinden beklenenler. Gece Kitapligi.
[35] Elmas, E. T., & Ogul, L. (2025). The effects of medicine and music therapy practices on human health. International Journal of Clinical Medicine Case Reports, 50(2), 003. https://doi.org/10.46998/IJCMCR.2025.50.001233
[36] Elmas, E. T., & Kaya, S. (2025). Biomechanical analysis of transtibial prosthesis designed for runners. Biomedical and Clinical Research Journal, 1(2).
[37] Elmas, E. T., & Oruc, Y. (2026). A novel mobile Bio-Eye-Tronic system based on the Elmas’s thermodynamic theory for cataract disease. Studies in Science of Science, 44(2). https://doi.org/10.5281/zenodo.18516267
[38] Elmas, E. T., & Cinibulak, M. A. (2025). Fundamental scientific and technical issues related with the hip replacement design and biomechanical analysis. Journal of Material Science and Nanotechnology.
[39] Elmas, E. T., & Kunduracioglu, I. (2025). A model for second law of thermodynamics, relationship between health, disease, aging, death processes and consciousness, nervous system and time. Global Journal of Research in Medical Sciences, 5(2), 1-6. https://doi.org/10.5281/zenodo.14973559
[40] Elmas, E. T., & Kunduracioglu, I. (2025). Metabolic heat production with energy transfer and laws of human thermodynamics: The energy balance of the human body. Global Journal of Research in Medical Sciences, 5(2), 7-14. https://doi.org/10.5281/zenodo.14973620
[41] Elmas, E. T., & Kunduracioglu, I. (2025). Artificial heart design and biomechanical analysis. Open Access Journal of Medicine and Healthcare, 1(1), 01-06.
[42] Elmas, E. T., & Kunduracioglu, I. (2025). Fundamentals of human vision system. Global Journal of Research in Medical Sciences, 5(2), 103-117. https://doi.org/10.5281/zenodo.15078754
[43] Elmas, E. T. (2025). Kitchen hood design & manufacturing project: 3D modeling, engineering calculations, and technical drawings for Igdir University Medico Social Building Dining Hall. Journal of Material Science and Nanotechnology, 1(1), 102.
[44] Elmas, E. T., & Kunduracioglu, I. (2025). Signal transduction system in neurons. International Journal of Research in Medical and Clinical Sciences, 3(1), 26-35.
[45] Elmas, E. T., & Kunduracioglu, I. (2025). An introduction to sound and sound perception system for human ear. International Journal of Research in Medical and Clinical Sciences, 3(1), 36-49.
[46] Elmas, E. T., & Kunduracioglu, I. (2025). Medical structure of the human respiratory system. International Journal of Research in Medical and Clinical Sciences, 3(1), 50-63.
[47] Elmas, E. T., & Kunduracioglu, I. (2025). Medical structure and hemodynamics of the human circulatory system. International Journal of Research in Medical and Clinical Sciences, 3(1), 64-81.
[48] Elmas, E. T., & Kunduracioglu, I. (2025). General aspects of advanced biomechanics. Biomedical Journal of Scientific & Technical Research, 61(5).
[49] Elmas, E. T., & Kunduracioglu, I. (2025). Conservation laws and the main physical parameters for advanced biomechanics. Biomedical Journal of Scientific & Technical Research, 61(5).
[50] Elmas, E. T., & Simsek, M. (2025). Bionic prosthetic robotic artificial hand design and biomechanics analysis. Journal of Medical Discoveries, 2(1).
[51] Elmas, E. T. (2025). Prosthetics, artificial limbs, implants and their biomedical applications. Journal of Surgery, 10, 11365. https://doi.org/10.29011/2575-9760.011365
[52] Elmas, E. T. (2025). An introduction to electrophysical properties of the human heart. Journal of Surgery, 10, 11364. https://doi.org/10.29011/2575-9760.011364
[53] Elmas, E. T. (2025). A brief information about cataract operation. European Journal of Science and Modern Technologies, 1(2), 61-66. https://doi.org/10.59324/ejsmt.2025.1(2).05
[54] Elmas, E. T. (2025). A brief information about blood sugar and diabetes management. ICON Journal of Applied Medical Sciences, 1(1), 1-5. https://doi.org/10.5281/zenodo.15870465
[55] Elmas, E. T., & Kunduracioglu, I. (2025). An introduction to the medical body mechanics and human muscles. Journal of Medical and Clinical Case Reports, 2(1). https://doi.org/10.61615/JMCCR/2025/APRIL027140418
[56] Elmas, E. T., & Kunduracioglu, I. (2025). Elastomechanics fundamentals for bones and fractures. Annals of Biotechnology & Biomedical Sciences, 1(1), 1-12.
[57] Elmas, E. T., & Oruc, Y. (2025). An alternative non-surgical cataract treatment method in medicine and ophthalmology; Medi-Ultrasound Eye-Tronic Method. Universal Library of Medical and Health Sciences, 3(3), 01-07. https://doi.org/10.70315/uloap.ulmhs.2025.0303001
[58] Elmas, E. T. (2024). System design and development of a novel unique neuro-physical medical treatment method for SMA-spinal muscular atrophy disease. Collective Journal of Neurology, 1, ART0037. https://doi.org/10.70107/collectjneurol-art0037
[59] Elmas, E. T. (2024). Design of bionic eye and artificial vision system; a unique project Mobile Bio-Eye-Tronic System. Collective Journal of Robotics AI, 1, ART0038. https://doi.org/10.70107/collectjroboticsai-art0038
[60] Elmas, E. T. (2025). Prospective characteristics of contemporary engineer: Contribution and role of the mechanical engineer to the organization management and productivity. In C. Machado & J. P. Davim (Eds.), Productivity and organizational management (2nd ed., Chapter 8). De Gruyter. https://doi.org/10.1515/9783112206775-008
[61] Elmas, E. T. (2025). Prospective characteristics of contemporary engineer: Contribution and role of the mechanical engineer to the organization management and productivity (2nd ed.). De Gruyter. https://doi.org/10.1515/9783112206775-008
[62] Elmas, E. T., & Simsek, M. (2025). Bionic prosthetic robotic artificial hand design and biomechanics analysis. Journal of Medical Discoveries, 2(1).
[63] Elmas, E. T., & Kaya, S. (2025). The effect of eye and vision on the body’s balance system. Biomedical Journal of Scientific & Technical Research, 61(5).
[64] Elmas, E. T., & Simsek, M. (2025). A novel unique neuro-physical medical treatment method for SMA-spinal muscular atrophy disease, paralyzed patients, ALS patients, MPS, SSPE, DMD patients and for similar neurological muscle diseases. Universal Library of Medical and Health Sciences, 3(3), 32-52. https://doi.org/10.70315/uloap.ulmhs.2025.0303005
[65] Elmas, E. T. (2026). Thermodynamic and mathematical model of human brain for neurodegenerative diseases; Alzheimer’s disease (AD) Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). International Journal of Science, Engineering and Technology, 14(1).
[66] Elmas, E. T. (2026). The exploration of Alzheimer’s disease, along with other neurodegenerative disorders like Parkinson’s and ALS, through the lens of thermodynamics and physical sciences. Gongcheng Kexue Xuebao, 11(2).
[67] Elmas, E. T. (2025). Applied Medi-Brain Energy-Tronic Treatment Method for the medical treatments of SMA-spinal muscular atrophy disease, paralyzed patients, ALS patients, MPS, SSPE, DMD patients. Journal of Engineering and Applied Sciences Technology. https://doi.org/10.47363/JEAST/2025(7)335
[68] Elmas, E. T. (2026). Scientific and technical introduction to Applied Medi-Brain Energy-Tronic Treatment Method - a novel and unique physiological, neuroengineering and neuroscientific medical treatment method. Journal of Psychology and Neuroscience, 8(1), 1-19. https://doi.org/10.47485/2693-2490.1144
[69] Elmas, E. T. (2026). Thermodynamics and energy transfer in medicine applications with archaeomusicology and music therapy. Studies in Science of Science, 44(1). https://doi.org/10.5281/zenodo.18130664
[70] Elmas, E. T., & Dag, I. (2026). Alzheimer hastaligi ve Parkinson, ALS gibi benzer nodejeneratif hastaliklarin termodinamik ve fizik bilimleri dahilinde incelenmesi. Studies in Science of Science, 44(1). https://doi.org/10.5281/zenodo.18302960
[71] Elmas, E. T. (2026). Bilim ve muhendislikte tip teknigi uygulama alanlarinin Turkiye ekonomisi yonunden degerlendirme ve analizi. Journal of Xidian University, 20. https://doi.org/10.5281/Zenodo.18276829
[72] Elmas, E. T. (2026). Thermodynamic energy transfer modeling of neurodegeneration with the Elmas’s Theory of Thermodynamics which is the main scientific approach for 5th law of thermodynamics. Research Paper, 8(3), 1-22. https://doi.org/10.5281/zenodo.19325343
[73] Elmas, E. T. (2026). Makina muhendisligi yaklasimi ile nodejeneratif hastaliklarin termodinamiksel analizi; Alzheimer, Parkinson ve ALS hastaliklari icin termodinamik model. In A. B. Demirpolat (Ed.), Makine muhendisliginde yeni nesil teknolojiler (Bolum 4). Vizetek Yayincilik. https://doi.org/10.54637/vizetek.9786253822194
[74] Elmas, E. T. (2026). Makina muhendisligi yaklasimi ile nodejeneratif hastaliklarin termodinamiksel analizi; matematiksel model ve literaturdeki klinik gozlemler. In A. B. Demirpolat (Ed.), Makine muhendisliginde yeni nesil teknolojiler (Bolum 5). Vizetek Yayincilik. https://doi.org/10.54637/vizetek.9786253822194
[75] Elmas, E. T. (2026). Multifaceted holistic medical health engineering combined with science and art. International Journal of Research in Medical and Clinical Sciences, 4(1), 91-102.
[76] Elmas, E. T. (2026). Bilim ve sanat ile cok yonlu butuncul yaklasim. Vizetek Yayincilik. https://doi.org/10.54637/vizetek.9786253822644
[77] Elmas, E. T. (2026). Cancer medical treatment in conjunction with the Elmas’s Theory of Thermodynamics which is the main scientific approach for 5th law of thermodynamics. Journal of Nanosciences Research & Reports. https://doi.org/10.47363/JNSRR/2026(8)186
[78] Elmas, E. T. (2026). Adaptation of AI simulation integrated artificial heart and cardiology applications with Elmas’s Theory of Thermodynamics. Journal of Cardiology and Vascular Insights, 2(2), 01-14.
[79] Elmas, E. T. (2026). Medical heat pipes - heat pipe applications in medical technique on the basis of Elmas’s Theory of Thermodynamics and 5th law of thermodynamics. Journal of Engineering and Applied Sciences Technology. https://doi.org/10.47363/JEAST/2026(8)352
[80] Elmas, E. T. (2026). Traditional diagnostic methods of Alzheimer’s disease and evaluation of Alzheimer’s diagnosis with blood tests. International Journal of Research in Medical and Clinical Sciences, 4(1), 133-146.
[81] Elmas, E. T. (2026). Science and art with a multifaceted and multidisciplinary holistic approach. Vizetek Yayincilik. https://doi.org/10.54637/vizetek.9786253822859
[82] Elmas, E. T. (2026). Elmas’s Energy-Tronic Medical Treatment Methods based on the principles of biomechatronics and neuro-physics in connection with the applications of BCI brain-computer interface for modeling of neurological diseases. Journal of Advanced Clinical Neuroscience Research, 2(2), 01-17.
[83] Elmas, E. T. (2026). DBS - deep brain stimulation application for Parkinson’s disease on the basis of Elmas’s Energy-Tronic System. Journal of Surgery and Surgical Procedures, 4(2), 1-11. https://doi.org/10.47485/3069-8154.1031
[84] Elmas, E. T. (2026). Engineering-based technological transformation in dentistry and endodontics and its impact on Turkiye’s competitiveness in the health tourism market. International Journal of Medical Science and Dental Health, 12(4), 109-122. https://doi.org/10.55640/ijmsdh-12-04-14
[85] Elmas, E. T. (2026). Application of Elmas’s Theory of Thermodynamics & 5th law of thermodynamics for design and optimization of ECMO (extracorporeal membrane oxygenation) machine and life support units. International Journal of Clinical Case Reports and Clinical Reviews, 1(1).
[86] Elmas, E. T. (2026). Diagnosis and treatment of internal bleeding with medical thermodynamics which is the medicine of the future. Biomedical Journal of Scientific & Technical Research, 65(3).
[87] Elmas, E. T. (2026). Design and optimization of mobile ECMO (extracorporeal membrane oxygenation) machine and life support units. International Journal of Research in Medical and Clinical Sciences, 4(1), 156-166.
[88] Elmas, E. T. (2026). Pancreatic cancer diagnosis and medical treatment - ELMAS Medi-Bio-Energy Tronic medical device system design study for pancreatic cancer diagnosis. Universal Library of Medical and Health Sciences, 4(2), 21-44. https://doi.org/10.70315/uloap.ulmhs.2026.0402004
[89] Elmas, E. T., ve ark. (2026). AI-enabled bionic eye and artificial vision system - AI-enabled Mobile Bio-Eye-Tronic System based on the scientific framework of Elmas’s Theory of Thermodynamics, 02-26.
[90] Elmas, E. T. (2026). Artificial blood model & ideal Super Blood model (optimized homeostasis) with Elmas’s Theory of Thermodynamics and 5th law of thermodynamics including hemodynamic principles. Journal of Clinical Case Reports, Medical Imaging and Health Sciences, 14(4).
[91] Elmas, E. T. (2026). Application of Elmas’s Theory of Thermodynamics & the fifth law of thermodynamics approach with bio-robotic resonance and thermodynamic interaction method for the medical diagnosis and treatment of colon cancer (colorectal cancer). American Journal of Medical Case Reports and Reviews, 5(5), 1-25.
[92] Elmas, E. T. (2026). Life support units including ECMO machine, artificial kidney (dialysis), artificial liver, artificial pancreas, artificial lung applications under Elmas’s operating system with integrated life support software Central Homeostasis Processor. Journal of Recent Advances in Nanomedicine & Nanotechnology, 2(1), 555578.
[93] Elmas, E. T. (2026). Engineering design and operational analysis of cardiopulmonary bypass (CPB) machines with the 5th law of thermodynamics and Elmas’s Theory of Thermodynamics. International Journal of Research in Medical and Health Sciences, 1(1), 01-10.
[94] Elmas, E. T. (2026). Designing a next-generation smart artificial cornea from the perspective of bio-robotic resonance and medical thermodynamics: A multidisciplinary engineering approach. Universal Library of Medical and Health Sciences, 4(2), 45-57. https://doi.org/10.70315/uloap.ulmhs.2026.0402005
[95] Elmas, E. T. (2026). Technical design study of a mobile portable (movable), home-type hemodialysis machine working as an artificial kidney. Journal of Internal Medicine Research & Reports. https://doi.org/10.47363/JIMRR/2026(5)155
[96] Elmas, E. T. (2026). The relationship and treatment of autoimmune diseases, particularly thyroid diseases, with stress: Bio-robotic resonance and thermodynamical interaction method and the use of the 5th law of thermodynamics within the scope of Elmas’s Theory of Thermodynamics. Journal of Psychology and Neuroscience, 8(3), 1-20.
[97] Eng, C., Yoshino, T., Ruiz-Garcia, E., ve ark. (2024). Colorectal cancer. The Lancet, 404(10449), 294-310. https://doi.org/10.1016/S0140-6736(24)00360-X
[98] Morgan, E., Arnold, M., Gini, A., ve ark. (2023). Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN. Gut, 72(2), 338-344. https://doi.org/10.1136/gutjnl-2022-327736
[99] Siegel, R. L., Giaquinto, A. N., & Jemal, A. (2024). Cancer statistics, 2024. CA: A Cancer Journal for Clinicians, 74(1), 12-49. https://doi.org/10.3322/caac.21820
[100] Darmadi, D., Mohammadian-Hafshejani, A., & Kheiri, S. (2025). Global disparities in colorectal cancer: Unveiling the present landscape of incidence and mortality rates, analyzing geographical variances, and assessing the Human Development Index. Journal of Preventive Medicine and Hygiene, 65(4), E499-E514. https://doi.org/10.15167/2421-4248/jpmh2024.65.4.3071
[101] Rawla, P., Sunkara, T., & Barsouk, A. (2019). Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Przeglad Gastroenterologiczny, 14(2), 89-103. https://doi.org/10.5114/pg.2018.81072
[102] Chu, S., Shi, X., Tian, Y., & Gao, F. (2022). pH-responsive polymer nanomaterials for tumor therapy. Frontiers in Oncology, 12, 855019. https://doi.org/10.3389/fonc.2022.855019
[103] Liu, Y., Si, L., Jiang, Y., ve ark. (2025). Design of pH-responsive nanomaterials based on the tumor microenvironment. International Journal of Nanomedicine, 20, 705-721. https://doi.org/10.2147/IJN.S504629
[104] Guo, S., Qiao, X., Ding, L., ve ark. (2025). pH-responsive magnetic Fe3O4 modified chitosan nanoparticles loaded with beta-acids to improve colorectal cancer treatment. Materials Today Bio, 34, 102151. https://doi.org/10.1016/j.mtbio.2025.102151
[105] Mokhtarzadeh, A., Hassanpour, S., Vahid, Z. F., ve ark. (2017). Nano-delivery system targeting to cancer stem cell cluster of differentiation biomarkers. Journal of Controlled Release, 266, 166-186. https://doi.org/10.1016/j.jconrel.2017.09.024
[106] Taher, M., Susanti, D., Haris, M. S., ve ark. (2023). PEGylated liposomes enhance the effect of cytotoxic drug: A review. Heliyon, 9(2), e13823. https://doi.org/10.1016/j.heliyon.2023.e13823
[107] Grunwald, B., Vandooren, J., Locatelli, E., ve ark. (2016). Matrix metalloproteinase-9 (MMP-9) as an activator of nanosystems for targeted drug delivery in pancreatic cancer. Journal of Controlled Release, 239, 39-48. https://doi.org/10.1016/j.jconrel.2016.08.016
[108] Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell, 141(1), 52-67. https://doi.org/10.1016/j.cell.2010.03.015
[109] Al-Saeedi, M., Steinebrunner, N., Kudlak, A., ve ark. (2023). Novel matrix metalloproteinase-9 (MMP-9) inhibitors in cancer treatment. International Journal of Molecular Sciences, 24(15), 12133. https://doi.org/10.3390/ijms241512133
[110] Chen, Y., Zhao, G., Li, P., ve ark. (2025). Applications of matrix metalloproteinase-9-related nanomedicines in tumors and vascular diseases. Pharmaceutics, 17(4), 479. https://doi.org/10.3390/pharmaceutics17040479
[111] Fu, Z., & Xiang, J. (2020). Aptamer-functionalized nanoparticles in targeted delivery and cancer therapy. International Journal of Molecular Sciences, 21(23), 9123. https://doi.org/10.3390/ijms21239123
[112] Narwade, M., Shaikh, A., Gajbhiye, K. R., Kesharwani, P., & Gajbhiye, V. (2023). Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery. Biomaterials Research, 27(1), 45. https://doi.org/10.1186/s40824-023-00365-y
[113] Camorani, S., Tortorella, S., Agnello, L., ve ark. (2022). Aptamer-functionalized nanoparticles mediate PD-L1 siRNA delivery for effective gene silencing in triple-negative breast cancer cells. Pharmaceutics, 14(10), 2225. https://doi.org/10.3390/pharmaceutics14102225
[114] Ozalp, V. C., Eyidogan, F., & Oktem, H. A. (2011). Aptamer-gated nanoparticles for smart drug delivery. Pharmaceuticals, 4(8), 1137-1157. https://doi.org/10.3390/ph4081137
[115] Zhu, G., Niu, G., & Chen, X. (2015). Aptamer-drug conjugates. Bioconjugate Chemistry, 26(11), 2186-2197. https://doi.org/10.1021/acs.bioconjchem.5b00291
[116] Vazquez-Gonzalez, M., & Willner, I. (2021). Aptamer-functionalized micro- and nanocarriers for controlled release. ChemNanoMat, 7(9), 963-979. https://doi.org/10.1002/cnma.202100024
[117] Parikh, A. R., Van Seventer, E. E., Siravegna, G., ve ark. (2021). Minimal residual disease detection using a plasma-only circulating tumor DNA assay in patients with colorectal cancer. JCO Precision Oncology, 5, PO.20.00349. https://doi.org/10.1200/PO.20.00349
[118] Taieb, J., Tougeron, D., Taly, V., ve ark. (2022). Using circulating tumor DNA in colorectal cancer: Current and evolving practices. Journal of Clinical Oncology, 40(24), 2818-2829. https://doi.org/10.1200/JCO.21.02615
[119] Faulkner, L. G., Howell, L. M., Pepper, C., ve ark. (2023). The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: A systematic review and meta-analysis. British Journal of Cancer, 128(2), 297-309. https://doi.org/10.1038/s41416-022-02017-9
[120] Tie, J., Cohen, J. D., Lahouel, K., ve ark. (2022). Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. New England Journal of Medicine, 386(24), 2261-2272. https://doi.org/10.1056/NEJMoa2200075
[121] Shim, H., Heo, S., Sun, J., ve ark. (2025). Clinical utility of monitoring circulating tumor DNA using a targeted next-generation sequencing panel in patients with colorectal cancer. Annals of Laboratory Medicine, 45(4), 450-458. https://doi.org/10.3343/alm.2024.0598
[122] Giansanti, D., & Morelli, S. (2025). Exploring the potential of digital twins in cancer treatment: A narrative review of reviews. Journal of Clinical Medicine, 14(10), 3574. https://doi.org/10.3390/jcm14103574
[123] Mollica, L., Leli, C., Sottotetti, F., ve ark. (2024). Digital twins: A new paradigm in oncology in the era of big data. ESMO Real World Data and Digital Oncology, 5, 100056. https://doi.org/10.1016/j.esmorw.2024.100056
[124] Kemkar, S., Tao, M., Ghosh, A., ve ark. (2024). Towards verifiable cancer digital twins: Tissue level modeling protocol for precision medicine. Frontiers in Physiology, 15, 1473125. https://doi.org/10.3389/fphys.2024.1473125
[125] Asghar, U. S., & Chung, H. C. (2025). Application of digital twins for personalized oncology. Nature Reviews Cancer. https://doi.org/10.1038/s41568-025-00850-7
[126] Bouriga, R., Bailleux, C., Gal, J., ve ark. (2025). Advances and critical aspects in cancer treatment development using digital twins. Briefings in Bioinformatics, 26, bbaf237. https://doi.org/10.1093/bib/bbaf237
[127] Sanchez-Peralta, L. F., Glover, B., Jha, D., & Pagador, J. B. (2024). Artificial intelligence for early diagnosis of colorectal cancer [Editorial]. Frontiers in Oncology, 14, 1495827. https://doi.org/10.3389/fonc.2024.1495827
[128] Boedtkjer, E., & Pedersen, S. F. (2020). The acidic tumor microenvironment as a driver of cancer. Annual Review of Physiology, 82, 103-126. https://doi.org/10.1146/annurev-physiol-021119-034627
[129] Estrella, V., ve ark. (2013). Acidity generated by the tumor microenvironment drives local invasion. Cancer Research, 73(5), 1524-1535. https://doi.org/10.1158/0008-5472.CAN-12-2796
[130] He, X., ve ark. (2018). Acidic tumor microenvironment: A target for smart cancer nano-theranostics. National Science Review, 5(2), 269-288. https://doi.org/10.1093/nsr/nwx062
[131] Li, W., ve ark. (2022). PEGylated cisplatin nanoparticles for treating colorectal cancer in a pH-responsive manner. Journal of Immunology Research, 2022, 8023915. https://doi.org/10.1155/2022/8023915
[132] Hurst, N. G., ve ark. (2007). Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients. British Journal of Cancer, 97(7), 971-977. https://doi.org/10.1038/sj.bjc.6603958
[133] Dragutinovic, V. V., Radonjic, N. V., Petronijevic, N. D., Tatic, S. B., Dimitrijevic, I. B., Radovanovic, N. S., & Krivokapic, Z. V. (2011). Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer. Molecular and Cellular Biochemistry, 355(1-2), 173-178. https://doi.org/10.1007/s11010-011-0851-0
[134] Tutton, M. G., ve ark. (2003). Use of plasma MMP-2 and MMP-9 levels as a surrogate for tumour expression in colorectal cancer patients. International Journal of Cancer, 107(4), 541-550. https://doi.org/10.1002/ijc.11436
[135] Huang, H. (2018). Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors, 18(10), 3249. https://doi.org/10.3390/s18103249
[136] Otero-Estevez, O., ve ark. (2015). Serum matrix metalloproteinase-9 in colorectal cancer family-risk population screening. Scientific Reports, 5, 13030. https://doi.org/10.1038/srep13030
[137] Kessenbrock, K., Plaks, V., & Werb, Z. (2010). Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell, 141(1), 52-67. https://doi.org/10.1016/j.cell.2010.03.015
[138] Chen, Y., ve ark. (2025). Applications of matrix metalloproteinase-9-related nanomedicines in tumors and vascular diseases. Pharmaceutics, 17(4), 479. https://doi.org/10.3390/pharmaceutics17040479
[139] Mahmoudian, F., ve ark. (2024). Aptamers as an approach to targeted cancer therapy. Cancer Cell International, 24, 108. https://doi.org/10.1186/s12935-024-03295-4
[140] Zhu, L., ve ark. (2023). Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer. Journal of Nanobiotechnology, 21, 182. https://doi.org/10.1186/s12951-023-01941-z
[141] Go, G., ve ark. (2021). PrPC aptamer conjugated-gold nanoparticles for targeted delivery of doxorubicin to colorectal cancer cells. International Journal of Molecular Sciences, 22(4), 1976. https://doi.org/10.3390/ijms22041976
[142] Pytlikova, S., ve ark. (2025). Dual thermo- and pH-responsive polymer nanoparticle assemblies for potential stimuli-controlled drug delivery. ACS Applied Bio Materials, 8(1), 271-284. https://doi.org/10.1021/acsabm.4c01167
[143] Biabanikhankahdani, R., ve ark. (2016). pH-responsive virus-like nanoparticles with enhanced tumour-targeting ligands for cancer drug delivery. Scientific Reports, 6, 37891. https://doi.org/10.1038/srep37891
[144] Rachamala, H. K., ve ark. (2025). Translational advances in lipid nanoparticle drug delivery systems for cancer therapy: Current status and future horizons. Pharmaceutics, 17(10), 1315. https://doi.org/10.3390/pharmaceutics17101315
[145] Ottaiano, A., ve ark. (2025). Genomic trajectories of colorectal cancer with choroidal metastasis: Longitudinal insights from tissue and liquid biopsy via next-generation sequencing. Frontiers in Genetics, 16, 1632580. https://doi.org/10.3389/fgene.2025.1632580
[146] Parigger, T., Gassner, F. J., Drothler, S., ve ark. (2024). Combined DNA analysis from stool and blood samples improves tumor tracking and assessment of clonal heterogeneity in localized rectal cancer patients. Technology in Cancer Research & Treatment, 23. https://doi.org/10.1177/15330338241252706
[147] Giansanti, D., & Morelli, S. (2025). Exploring the potential of digital twins in cancer treatment: A narrative review of reviews. Journal of Clinical Medicine, 14(10), 3574. https://doi.org/10.3390/jcm14103574
[148] Asghar, U. S., & Chung, C. (2025). Application of digital twins for personalized oncology. Nature Reviews Cancer, 25, 823-825. https://doi.org/10.1038/s41568-025-00850-7
[149] Lee, C. J., ve ark. (2026). The dysadherin/carbonic anhydrase 9 axis shapes an acidic tumor microenvironment to promote colorectal cancer progression. Signal Transduction and Targeted Therapy, 11(1), 1-18. https://doi.org/10.1038/s41392-025-02543-x
[150] Chu, S., ve ark. (2022). pH-responsive polymer nanomaterials for tumor therapy. Frontiers in Oncology, 12, 855019. https://doi.org/10.3389/fonc.2022.855019
[151] Liu, Y., ve ark. (2025). Design of pH-responsive nanomaterials based on the tumor microenvironment. International Journal of Nanomedicine, 20, 705-721. https://doi.org/10.2147/IJN.S504629
[152] Guo, S., ve ark. (2025). pH-responsive magnetic Fe3O4 modified chitosan nanoparticles loaded with beta-acids to improve colorectal cancer treatment. Materials Today Bio, 34, 102151. https://doi.org/10.1016/j.mtbio.2025.102151
[153] Park, D., ve ark. (2024). Aptamer-based smart targeting and spatial trigger-response drug-delivery systems for anticancer therapy. Biomedicines, 12(1), 187. https://doi.org/10.3390/biomedicines12010187
[154] Wen, X., ve ark. (2024). Development of an aptamer capable of multidrug resistance reversal for tumor combination chemotherapy. Proceedings of the National Academy of Sciences USA, 121(15), e2321116121. https://doi.org/10.1073/pnas.2321116121
[155] Narwade, M., ve ark. (2023). Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery. Biomaterials Research, 27(1), 42. https://doi.org/10.1186/s40824-023-00365-y
[156] Ullah, F., ve ark. (2022). Formulation development and characterization of pH responsive polymeric nano-pharmaceuticals for targeted delivery of anti-cancer drug (methotrexate). Frontiers in Pharmacology, 13, 911771. https://doi.org/10.3389/fphar.2022.911771
[157] Kordkatouli, M., ve ark. (2024). Recent progress in nanoparticle-driven drug delivery strategies for cancer therapy: Focus on colorectal cancer. Zahedan Journal of Research in Medical Sciences, 27(1), e158109. https://doi.org/10.5812/zjrms-158109
[158] Suzuki, T., Suzuki, T., Yoshimura, Y., ve ark. (2020). Detection of circulating tumor DNA in patients of operative colorectal and gastric cancers. Oncotarget, 11(34), 3198-3207. https://doi.org/10.18632/oncotarget.27682
[159] Hansen, E., & Read, A. F. (2020). Modifying adaptive therapy to enhance competitive suppression. Cancers, 12(12), 3556. https://doi.org/10.3390/cancers12123556
[160] Mollica, L., ve ark. (2024). Digital twins: A new paradigm in oncology in the era of big data. ESMO Real World Data and Digital Oncology, 5, 100056. https://doi.org/10.1016/j.esmorw.2024.100056
[161] Elmas, E. T. (2026). Elmas thermodynamic theory and FM-modulated biorobotic resonance approach for the early diagnosis and treatment of pancreatic cancer. Frontiers in Research, 6(3), 186-203. https://doi.org/10.71350/30624533144
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