Immunosuppressive drugs and cancer risk

Sakshi M. Karmore; Gaurav S. Mude; Pranali R. Date

doi:10.31893/multirev.2024260

Keywords:

Abstract

The use of immunosuppressive medications is an area of interest for organ transplantation. These medications have been repurposed for the treatment of cancer in recent years. In the context of cancer therapy, the use of immunosuppressive medications such as cyclosporine, tacrolimus, sirolimus, mycophenolate acid mofetil (MMF), mycophenolate, and azathioprine is discussed. Treatment for cancer frequently includes methods designed to use the immune system to find and destroy cancer cells. Cancer cells can, however, avoid immune surveillance and eradication because the tumor microenvironment frequently has immune-suppressive components. Drugs that suppress the immune system, which were initially designed to avoid organ rejection, have demonstrated potential for obstructing these inhibitory pathways and boosting antitumour immune responses. Tacrolimus and cyclosporine, two immunosuppressive medications frequently used in transplantation, have potential anticancer effects. The immune system and stifling tumor-promoting inflammatory responses, can prevent tumor growth, angiogenesis, and metastasis. Another immunosuppressive drug, sirolimus, has shown anticancer effects by reducing angiogenesis and tumor cell growth while promoting immune-mediated tumors. Mycophenolate medicines, such as MMF and mycophenolate, have strong immunosuppressive properties. By inhibiting the enzymes responsible for purine production, these enzymes aim to inhibit lymphocyte proliferation. By altering immune cell function and reducing tumor growth, these medications have demonstrated promise in the treatment of cancer. Azathioprine, a medication that suppresses the immune system and is frequently used to treat autoimmune illnesses, has also been investigated as a possible cancer treatment. Although immunosuppressive medications have potential in the treatment of cancer, their usage needs to be carefully addressed due to potential side effects and the delicate balance between immune suppression and antitumour action. The immune system plays a crucial role in identifying and eliminating abnormal cells, including those associated with cancer.
References
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How to cite

Karmore, S. M., Mude, G. S., & Date, P. R. (2024). Immunosuppressive drugs and cancer risk. Multidisciplinary Reviews, 7(11), 2024260. https://doi.org/10.31893/multirev.2024260

[1] Adams, D. M., Trenor, C. C., Hammill, A. M., Vinks, A. A., Patel, M. N., Chaudry, G., Wentzel, M. S., Mobberley-Schuman, P. S., Campbell, L. M., Brookbank, C., Gupta, A., Chute, C., Eile, J., McKenna, J., Merrow, A. C., Fei, L., Hornung, L., Seid, M., Dasgupta, A. R., … Azizkhan, R. G. (2016). Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies. Pediatrics, 137(2), e20153257. https://doi.org/10.1542/peds.2015-3257

[2] Azathioprine-Induced Severe Bone Marrow Suppression | Case Reports in Clinical Practice. (n.d.). Retrieved September 5, 2023, from https://crcp.tums.ac.ir/index.php/crcp/article/view/231

[3] Bilbao, I., Salcedo, M., Gómez, M. A., Jimenez, C., Castroagudín, J., Fabregat, J., Almohalla, C., Herrero, I., Cuervas-Mons, V., Otero, A., Rubín, A., Miras, M., Rodrigo, J., Serrano, T., Crespo, G., De la Mata, M., Bustamante, J., Gonzalez-Dieguez, M. L., Moreno, A., … EVEROLIVER study group. (2015). Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain. Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 21(8), 1056–1065. https://doi.org/10.1002/lt.24172

[4] Björnsson, E. S., Gu, J., Kleiner, D. E., Chalasani, N., Hayashi, P. H., Hoofnagle, J. H., & DILIN Investigators. (2017). Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes. Journal of Clinical Gastroenterology, 51(1), 63–69. https://doi.org/10.1097/MCG.0000000000000568

[5] Borel, J. F., Feurer, C., Gubler, H. U., & Stähelin, H. (1976). Biological effects of cyclosporin A: A new antilymphocytic agent. Agents and Actions, 6(4), 468–475. https://doi.org/10.1007/BF01973261

[6] Broen, J. C. A., & van Laar, J. M. (2020). Mycophenolate mofetil, azathioprine and tacrolimus: Mechanisms in rheumatology. Nature Reviews. Rheumatology, 16(3), 167–178. https://doi.org/10.1038/s41584-020-0374-8

[7] Cangemi, M., Montico, B., Faè, D. A., Steffan, A., & Dolcetti, R. (2019). Dissecting the Multiplicity of Immune Effects of Immunosuppressive Drugs to Better Predict the Risk of de novo Malignancies in Solid Organ Transplant Patients. Frontiers in Oncology, 9, 160. https://doi.org/10.3389/fonc.2019.00160

[8] Casanovas, T., Argudo, A., & Peña-Cala, M. C. (2011). Everolimus in clinical practice in long-term liver transplantation: An observational study. Transplantation Proceedings, 43(6), 2216–2219. https://doi.org/10.1016/j.transproceed.2011.06.015

[9] Chakkera, H., Kudva, Y., & Kaplan, B. (2017). Calcineurin Inhibitors: Pharmacologic Mechanisms Impacting Both Insulin Resistance and Insulin Secretion Leading to Glucose Dysregulation and Diabetes Mellitus. Clinical Pharmacology & Therapeutics, 101(1), 114–120. https://doi.org/10.1002/cpt.546

[10] Chitty, J. (2017). Classical and rational approaches to antifungal drug design [PhD Thesis, The University of Queensland]. https://doi.org/10.14264/uql.2017.1070

[11] Denman, A. M. (1982). Immunosuppression and the rheumatic diseases. Annals of the Rheumatic Diseases, 41(Suppl 1), 3–8.

[12] Dias-Polak, D., Bergman, R., & Avitan-Hersh, E. (2019). Mycophenolate mofetil therapy in adult patients with recalcitrant atopic dermatitis. The Journal of Dermatological Treatment, 30(1), 49–51. https://doi.org/10.1080/09546634.2018.1468068

[13] Dordal Culla, M. T., Herrera-Lasso Regás, V., Martí-Garrido, J., Rodríguez Cumplido, D., Vázquez-Revuelta, P., & Lleonart Bellfill, R. (2020). Treating COVID-19: Review of Drug Hypersensitivity Reactions. Journal of Investigational Allergology & Clinical Immunology, 30(6), 385–399. https://doi.org/10.18176/jiaci.0588

[14] Fröhlich, E. (2019). Understanding and Preventing Adverse Effects of Tacrolimus Metabolization in Transplant Patients. Current Drug Metabolism, 20(13), 1039–1040. https://doi.org/10.2174/1389200219666180806154433

[15] Fuggle, N. R., Bragoli, W., Mahto, A., Glover, M., Martinez, A. E., & Kinsler, V. A. (2015). The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring. Journal of the American Academy of Dermatology, 72(1), 108–114. https://doi.org/10.1016/j.jaad.2014.08.048

[16] Horneff, G. (2015). Safety of biologic therapies for the treatment of juvenile idiopathic arthritis. Expert Opinion on Drug Safety, 14(7), 1111–1126. https://doi.org/10.1517/14740338.2015.1042453

[17] Jouve, T., Noble, J., Rostaing, L., & Malvezzi, P. (2019). An update on the safety of tacrolimus in kidney transplant recipients, with a focus on tacrolimus minimization. Expert Opinion on Drug Safety, 18(4), 285–294. https://doi.org/10.1080/14740338.2019.1599858

[18] Kalt, D. A. (2017). Tacrolimus: A Review of Laboratory Detection Methods and Indications for Use. Laboratory Medicine, 48(4), e62–e65. https://doi.org/10.1093/labmed/lmx056

[19] Kaltenborn, A., & Schrem, H. (2013). Mycophenolate mofetil in liver transplantation: A review. Annals of Transplantation, 18, 685–696. https://doi.org/10.12659/AOT.889299

[20] Kemmner, S., Guba, M. O., Schönermarck, U., Stangl, M., & Fischereder, M. (2020). Cyclosporine as a preferred calcineurin inhibitor in renal allograft recipients with COVID-19 infection. Kidney International, 98(2), 507–508. https://doi.org/10.1016/j.kint.2020.05.024

[21] Liddicoat, A. M., & Lavelle, E. C. (2019). Modulation of innate immunity by cyclosporine A. Biochemical Pharmacology, 163, 472–480. https://doi.org/10.1016/j.bcp.2019.03.022

[22] Masi, S., Uliana, M., Gesi, M., Taddei, S., & Virdis, A. (2019). Drug-induced hypertension: Know the problem to know how to deal with it. Vascular Pharmacology, 115, 84–88. https://doi.org/10.1016/j.vph.2019.02.002

[23] Merkel, S., Mogilevskaja, N., Mengel, M., Haller, H., & Schwarz, A. (2006). Side Effects of Sirolimus. Transplantation Proceedings, 38(3), 714–715. https://doi.org/10.1016/j.transproceed.2006.01.044

[24] Moes, D. J. A. R., Guchelaar, H.-J., & de Fijter, J. W. (2015). Sirolimus and everolimus in kidney transplantation. Drug Discovery Today, 20(10), 1243–1249. https://doi.org/10.1016/j.drudis.2015.05.006

[25] Moes, D. J. A. R., Press, R. R., den Hartigh, J., van der Straaten, T., de Fijter, J. W., & Guchelaar, H.-J. (2012). Population pharmacokinetics and pharmacogenetics of everolimus in renal transplant patients. Clinical Pharmacokinetics, 51(7), 467–480. https://doi.org/10.2165/11599710-000000000-00000

[26] Montante, A., Le Bras, A., Pagnoux, C., Perrodeau, E., Ravaud, P., Terrier, B., Guillevin, L., Durand-Zaleski, I., & French Vasculitis Study Group. (2019). Cost-effectiveness of rituximab versus azathioprine for maintenance treatment in antineutrophil cytoplasmic antibody-associated vasculitis. Clinical and Experimental Rheumatology, 37 Suppl 117(2), 137–143.

[27] Pal, P., Giri, P. P., & Sinha, R. (2019). Cyclosporine in Resistant Systemic Arthritis—A Cheaper Alternative to Biologics. Indian Journal of Pediatrics, 86(7), 590–594. https://doi.org/10.1007/s12098-019-02912-9

[28] Park, H. (2011). The Emergence of Mycophenolate Mofetilin Dermatology. The Journal of Clinical and Aesthetic Dermatology, 4(1), 18–27.

[29] Pradier, A., Papaserafeim, M., Li, N., Rietveld, A., Kaestel, C., Gruaz, L., Vonarburg, C., Spirig, R., Puga Yung, G. L., & Seebach, J. D. (2019). Small-Molecule Immunosuppressive Drugs and Therapeutic Immunoglobulins Differentially Inhibit NK Cell Effector Functions in vitro. Frontiers in Immunology, 10, 556. https://doi.org/10.3389/fimmu.2019.00556

[30] Reyes, A., Mohanty, A., Pharaon, R., & Massarelli, E. (2023). Association between Immunosuppressive Therapy Utilized in the Treatment of Autoimmune Disease or Transplant and Cancer Progression. Biomedicines, 11(1), Article 1. https://doi.org/10.3390/biomedicines11010099

[31] Risk Factors: Immunosuppression - NCI (nciglobal,ncienterprise). (2015, April 29). [CgvArticle]. https://www.cancer.gov/about-cancer/causes-prevention/risk/immunosuppression

[32] Ross, K. (2007). For organ transplant recipients, cancer threatens long-term survival. Journal of the National Cancer Institute, 99(6), 421–422. https://doi.org/10.1093/jnci/djk141

[33] Sagcal-Gironella, A. C. P., Fukuda, T., Wiers, K., Cox, S., Nelson, S., Dina, B., Sherwin, C. M. T., Klein-Gitelman, M. S., Vinks, A. A., & Brunner, H. I. (2011). Pharmacokinetics and pharmacodynamics of mycophenolic acid and their relation to response to therapy of childhood-onset systemic lupus erythematosus. Seminars in Arthritis and Rheumatism, 40(4), 307–313. https://doi.org/10.1016/j.semarthrit.2010.05.007

[34] Saliba, F., Dharancy, S., Lorho, R., Conti, F., Radenne, S., Neau-Cransac, M., Hurtova, M., Hardwigsen, J., Calmus, Y., & Dumortier, J. (2011). Conversion to everolimus in maintenance liver transplant patients: A multicenter, retrospective analysis. Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 17(8), 905–913. https://doi.org/10.1002/lt.22292

[35] Setlai, B. P., Hull, R., Bida, M., Durandt, C., Mulaudzi, T. V., Chatziioannou, A., & Dlamini, Z. (2022). Immunosuppressive Signaling Pathways as Targeted Cancer Therapies. Biomedicines, 10(3), 682. https://doi.org/10.3390/biomedicines10030682

[36] Shin, H. S., Grgic, I., & Chandraker, A. (2019). Novel Targets of Immunosuppression in Transplantation. Clinics in Laboratory Medicine, 39(1), 157–169. https://doi.org/10.1016/j.cll.2018.10.008

[37] Sprague, R. G. (1950). OBSERVATIONS ON THE PHYSIOLOGIC EFFECTS OF CORTISONE AND ACTH IN MAN. Archives of Internal Medicine, 85(2), 199. https://doi.org/10.1001/archinte.1950.00230080003001

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[39] Tönshoff, B., David-Neto, E., Ettenger, R., Filler, G., van Gelder, T., Goebel, J., Kuypers, D. R. J., Tsai, E., Vinks, A. A., Weber, L. T., & Zimmerhackl, L. B. (2011). Pediatric aspects of therapeutic drug monitoring of mycophenolic acid in renal transplantation. Transplantation Reviews (Orlando, Fla.), 25(2), 78–89. https://doi.org/10.1016/j.trre.2011.01.001

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