Preprint / Version 1

Investigating Conventional and Personalized Approaches to Cancer Therapeutics

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  • Jordan Lee Palo Alto High School

DOI:

https://doi.org/10.58445/rars.1782

Keywords:

Cancer, Personalized Medicine, Conventional Treatment, Cancer Therapy, CAR-T, Immune Checkpoint Inhibitor, Radiation Therapy, Chemotherapy, Breast Cancer

Abstract

Cancer continues to be a destructive force in our society, with an estimated 1.9 million diagnosed cancer cases in 2024 (American Cancer Society, 2024). With its prevalence in society, it is increasingly important that we continue to advance the field of treatment to attempt to cure this terrible disease. This paper aims to better understand the different types of conventional and personalized therapies for cancer treatment and the pros and cons of each type of treatment. Specifically, the paper explores two types of conventional cancer therapeutics, chemotherapy and radiation therapy, and two types of personalized cancer therapeutics, immune checkpoint inhibitors and CAR-T. For each of the four treatments, the paper details how they combat cancer by describing the underlying biological mechanisms, situations in which they are implemented for therapy, and their benefits and limitations. Lastly, the paper touches on the use of all four of these cancer treatments in the use case of breast cancer, discussing integrative therapy in practice. The future of cancer treatment requires a thorough understanding of the underlying mechanisms of this disease to push innovation and find a cure. As research advances and technology evolves, we move closer to a world where effective and transformative treatment offers hope for every patient.

References

Abreu, T. R., Fonseca, N. A., Gonçalves, N., & Moreira, J. N. (2020). Current challenges and emerging opportunities of CAR-T cell therapies. Journal of Controlled Release: Official Journal of the Controlled Release Society, 319, 246–261. https://doi.org/10.1016/j.jconrel.2019.12.047

American Cancer Society. (2022, March 1). CAR T-cell Therapy and Its Side Effects | American Cancer Society [03/01/2022]. https://www.cancer.org/cancer/managing-cancer/treatment-types/immunotherapy/car-t-cell1.html

American Cancer Society. (2024). Cancer Facts & Figures 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html

Anand, U., Dey, A., Chandel, A. K. S., Sanyal, R., Mishra, A., Pandey, D. K., De Falco, V., Upadhyay, A., Kandimalla, R., Chaudhary, A., Dhanjal, J. K., Dewanjee, S., Vallamkondu, J., & Pérez de la Lastra, J. M. (2022). Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes & Diseases, 10(4), 1367–1401. https://doi.org/10.1016/j.gendis.2022.02.007

Arruebo, M., Vilaboa, N., Sáez-Gutierrez, B., Lambea, J., Tres, A., Valladares, M., & González-Fernández, Á. (2011). Assessment of the Evolution of Cancer Treatment Therapies. Cancers, 3(3), 3279–3330. https://doi.org/10.3390/cancers3033279

Bashir, D. (2023). Chemotherapy for Cancer: What It Is and How It Works. OSF. https://doi.org/10.31219/osf.io/7wk98

Baskar, R., Lee, K. A., Yeo, R., & Yeoh, K.-W. (2012). Cancer and Radiation Therapy: Current Advances and Future Directions. International Journal of Medical Sciences, 9(3), 193–199. https://doi.org/10.7150/ijms.3635

Bedognetti, D., Maccalli, C., Al Bader, S. B. J., Marincola, F. M., & Seliger, B. (2016). Checkpoint Inhibitors and Their Application in Breast Cancer. Breast Care, 11(2), 108–115. https://doi.org/10.1159/000445335

Bentzen, S. (2006). Preventing or reducing late side effects of radiation therapy: Radiobiology meets molecular pathology | Nature Reviews Cancer. Nature Reviews Cancer, 6, 702–713. https://doi.org/10.1038/nrc1950

Bertram, J. S. (2000). The molecular biology of cancer. Molecular Aspects of Medicine, 21(6), 167–223. https://doi.org/10.1016/S0098-2997(00)00007-8

Bingham, C. A. (1978). The Cell Cycle and Cancer Chemotherapy. The American Journal of Nursing, 78(7), 1201–1205. https://doi.org/10.2307/3461977

Bortfeld, T., & Jeraj, R. (2011). The physical basis and future of radiation therapy. British Journal of Radiology, 84(1002), 485–498. https://doi.org/10.1259/bjr/86221320

Campbell, L. L., & Polyak, K. (2007). Breast tumor heterogeneity: Cancer stem cells or clonal evolution? Cell Cycle (Georgetown, Tex.), 6(19), 2332–2338. https://doi.org/10.4161/cc.6.19.4914

Chakraborty, S., & Rahman, T. (2012). The difficulties in cancer treatment. Ecancermedicalscience, 6, ed16. https://doi.org/10.3332/ecancer.2012.ed16

Cheng, T., & Zhan, X. (2017). Pattern recognition for predictive, preventive, and personalized medicine in cancer. EPMA Journal, 8(1), 51–60. https://doi.org/10.1007/s13167-017-0083-9

Chidambaram, M., Manavalan, R., & Kathiresan, K. (2011). Nanotherapeutics to Overcome Conventional Cancer Chemotherapy Limitations. Journal of Pharmacy & Pharmaceutical Sciences, 14(1), Article 1. https://doi.org/10.18433/J30C7D

Connal, S., Cameron, J. M., Sala, A., Brennan, P. M., Palmer, D. S., Palmer, J. D., Perlow, H., & Baker, M. J. (2023). Liquid biopsies: The future of cancer early detection. Journal of Translational Medicine, 21(1), 118. https://doi.org/10.1186/s12967-023-03960-8

Connors, T. A. (1974). Alkylating agents. Medicinal Chemistry, 141–171. https://doi.org/10.1007/3-540-06873-2_16

Eifel, P. J. (2017). Role of radiation therapy. Best Practice & Research Clinical Obstetrics & Gynaecology, 41, 118–125. https://doi.org/10.1016/j.bpobgyn.2016.11.005

Gabizon, A. A. (1995). Liposome circulation time and tumor targeting: Implications for cancer chemotherapy. Advanced Drug Delivery Reviews, 16(2), 285–294. https://doi.org/10.1016/0169-409X(95)00030-B

Ganesh, K., & Massagué, J. (2021). Targeting metastatic cancer. Nature Medicine, 27(1), 34–44. https://doi.org/10.1038/s41591-020-01195-4

Gaynor, N., Crown, J., & Collins, D. M. (2022). Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. Seminars in Cancer Biology, 79, 44–57. https://doi.org/10.1016/j.semcancer.2020.06.016

Guimaraes, D. P., & Hainaut, P. (2002). TP53: A key gene in human cancer. Biochimie, 84(1), 83–93. https://doi.org/10.1016/S0300-9084(01)01356-6

Hajdu, S. I. (2011). A note from history: Landmarks in history of cancer, part 1. Cancer, 117(5), 1097–1102. https://doi.org/10.1002/cncr.25553

Han, X., Li, H., Zhou, D., Chen, Z., & Gu, Z. (2020). Local and Targeted Delivery of Immune Checkpoint Blockade Therapeutics | Accounts of Chemical Research. Accounts of Chemical Research, 53(11), 2521–2533. https://doi.org/10.1021/acs.accounts.0c00339

Hashim, D., Boffetta, P., La Vecchia, C., Rota, M., Bertuccio, P., Malvezzi, M., & Negri, E. (2016). The global decrease in cancer mortality: Trends and disparities. Annals of Oncology, 27(5), 926–933. https://doi.org/10.1093/annonc/mdw027

Heppner, G. H. (1984). Tumor heterogeneity. Cancer Research, 44(6), 2259–2265.

Huh, H. D., & Kim, S. (2020). History of Radiation Therapy Technology. Progress in Medical Physics, 31(3), 124–134. https://doi.org/10.14316/pmp.2020.31.3.124

Jakka, S., & Rossbach, M. (2013). An economic perspective on personalized medicine. The HUGO Journal, 7(1), 1. https://doi.org/10.1186/1877-6566-7-1

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science, 337(6096), 816–821. https://doi.org/10.1126/science.1225829

Johnson, D. B., Sullivan, R. J., & Menzies, A. M. (2017). Immune checkpoint inhibitors in challenging populations. Cancer, 123(11), 1904–1911. https://doi.org/10.1002/cncr.30642

Johnson, D. G., & Walker, C. L. (1999). Cyclins and cell cycle checkpoints. Annual Review of Pharmacology and Toxicology, 39, 295–312. https://doi.org/10.1146/annurev.pharmtox.39.1.295

Kaufmann, W. K., & Paules, R. S. (1996). DNA damage and cell cycle checkpoints. The FASEB Journal, 10(2), 238–247. https://doi.org/10.1096/fasebj.10.2.8641557

Kennedy, K. A., Teicher, B. A., Rockwell, S., & Sartorelli, A. C. (1980). The hypoxic tumor cell: A target for selective cancer chemotherapy. Biochemical Pharmacology, 29(1), 1–8. https://doi.org/10.1016/0006-2952(80)90235-X

Khan, U., & Ghazanfar, H. (2018). Chapter Three—T Lymphocytes and Autoimmunity. In L. Galluzzi & N.-P. Rudqvist (Eds.), International Review of Cell and Molecular Biology (Vol. 341, pp. 125–168). Academic Press. https://doi.org/10.1016/bs.ircmb.2018.05.008

Khosravi-Far, R., & Der, C. J. (1994). The Ras signal transduction pathway. Cancer and Metastasis Reviews, 13(1), 67–89. https://doi.org/10.1007/BF00690419

Kiyotani, K., Toyoshima, Y., & Nakamura, Y. (2021). Personalized immunotherapy in cancer precision medicine. Cancer Biology & Medicine, 18(4), 955–965. https://doi.org/10.20892/j.issn.2095-3941.2021.0032

Krogsgaard, M., & Davis, M. M. (2005). How T cells “see” antigen. Nature Immunology, 6(3), 239–245. https://doi.org/10.1038/ni1173

Lee, L., Gupta, M., & Sahasranaman, S. (2016). Immune Checkpoint inhibitors: An introduction to the next-generation cancer immunotherapy. The Journal of Clinical Pharmacology, 56(2), 157–169. https://doi.org/10.1002/jcph.591

Martincorena, I., & Campbell, P. J. (2015). Somatic mutation in cancer and normal cells. Science, 349(6255), 1483–1489. https://doi.org/10.1126/science.aab4082

Moffitt Cancer Center. (2024). CAR T-Cell Therapy for Leukemia. Moffitt. https://www.moffitt.org/cancers/leukemia/treatment/car-t-therapy-for-leukemia/

Mohanty, R., Chowdhury, C. R., Arega, S., Sen, P., Ganguly, P., & Ganguly, N. (2019). CAR T cell therapy: A new era for cancer treatment (Review). Oncology Reports, 42(6), 2183–2195. https://doi.org/10.3892/or.2019.7335

National Cancer Institute. (2017, July 31). Types of Cancer Treatment—NCI (nciglobal,ncienterprise) [cgvMiniLanding]. https://www.cancer.gov/about-cancer/treatment/types

National Cancer Institute. (2022, May 13). The Cancer Genome Atlas Program (TCGA)—NCI (nciglobal,ncienterprise) [cgvMiniLanding]. https://www.cancer.gov/ccg/research/genome-sequencing/tcga

Norton, A. E., & Broyles, A. D. (2017). Management of Children with Hypersensitivity to Antibiotics and Monoclonal Antibodies. Immunology and Allergy Clinics of North America, 37(4), 713–725. https://doi.org/10.1016/j.iac.2017.07.005

Phillips, K. A., Deverka, P. A., Hooker, G. W., & Douglas, M. P. (2018). Genetic Test Availability And Spending: Where Are We Now? Where Are We Going? Health Affairs, 37(5), 710–716. https://doi.org/10.1377/hlthaff.2017.1427

Richards, R. I. (2001). Fragile and unstable chromosomes in cancer: Causes and consequences. Trends in Genetics, 17(6), 339–345. https://doi.org/10.1016/S0168-9525(01)02303-4

Rubin, H. (1990). The significance of biological heterogeneity. Cancer Metastasis Reviews, 9(1), 1–20. https://doi.org/10.1007/BF00047585

Sabatier, R., Gonçalves, A., & Bertucci, F. (2014). Personalized medicine: Present and future of breast cancer management. Critical Reviews in Oncology/Hematology, 91(3), 223–233. https://doi.org/10.1016/j.critrevonc.2014.03.002

Scagliotti, G., & Selvaggi, G. (2016). Antimetabolites and cancer: Emerging data with a focus on antifolates: Expert Opinion on Therapeutic Patents: Vol 16, No 2. Expert Opinion on Therapeutic Patents, 16(2), 189–200. https://doi.org/10.1517/13543776.16.2.189

Sharpe, M., & Mount, N. (2015). Genetically modified T cells in cancer therapy: Opportunities and challenges. Disease Models & Mechanisms, 8(4), 337–350. https://doi.org/10.1242/dmm.018036

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

Singh, D. N., Daripelli, S., Elamin Bushara, M. O., Polevoy, G. G., & Prasanna, M. (2023). Genetic Testing for Successful Cancer Treatment. Cureus, 15(12), e49889. https://doi.org/10.7759/cureus.49889

Sterner, R. C., & Sterner, R. M. (2021). CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer Journal, 11(4), 1–11. https://doi.org/10.1038/s41408-021-00459-7

Sun, Y., Liu, Y., Ma, X., & Hu, H. (2021). IJMS | Free Full-Text | The Influence of Cell Cycle Regulation on Chemotherapy. International Journal of Molecular Sciences, 22(13), 6923.

Trayes, K., & Cokenakes, S. (2021). Breast Cancer Treatment | AAFP. American Family Physician, 104(2), 171–178.

Twombly, R. (2005). Cancer Surpasses Heart Disease as Leading Cause of Death for All But the Very Elderly. JNCI: Journal of the National Cancer Institute, 97(5), 330–331. https://doi.org/10.1093/jnci/97.5.330

van den Boogaard, W. M. C., Komninos, D. S. J., & Vermeij, W. P. (2022). Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers, 14(3), Article 3. https://doi.org/10.3390/cancers14030627

Veazey, K. (2021, October 29). What are some of the most common chemo drugs? What to Know about the Most Common Chemotherapy Drugs. https://www.medicalnewstoday.com/articles/most-common-chemo-drugs

Verma, M. (2012). Personalized Medicine and Cancer. Journal of Personalized Medicine, 2(1), Article 1. https://doi.org/10.3390/jpm2010001

Wang, X., Zhang, H., & Chen, X. (2019). Drug resistance and combating drug resistance in cancer. Cancer Drug Resistance, 2(2), 141–160. https://doi.org/10.20517/cdr.2019.10

Wei, S., Duffy, C., & Allison, J. (2018). Fundamental Mechanisms of Immune Checkpoint Blockade Therapy | Cancer Discovery | American Association for Cancer Research. Cancer Discovery, 8(9), 1069–1086. https://doi.org/10.1158/2159-8290.CD-18-0367

Weinberg, R. A. (1996). How Cancer Arises. Scientific American, 275(3), 62–70.

West, H. (Jack). (2015). Immune Checkpoint Inhibitors. JAMA Oncology, 1(1), 115. https://doi.org/10.1001/jamaoncol.2015.0137

Yang, Y.-H., Liu, J.-W., Lu, C., & Wei, J.-F. (2022). CAR-T Cell Therapy for Breast Cancer: From Basic Research to Clinical Application. International Journal of Biological Sciences, 18(6), 2609–2626. https://doi.org/10.7150/ijbs.70120

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2024-10-18