A network meta-analysis of anorexia treatments in disease and old age: pharmacogenomics, the gut-brain axis and artificial neural nets. Where are we?

Anorexia affects millions of people worldwide, and treatments vary widely, with no definitive treatment guidelines. A network meta-analysis compared and contrasted existing treatments for chronically ill and elderly patients. EMBASE, MEDLINE, PubMed, Cochrane, and clinicaltrials.gov were searched for articles reporting weight/body mass index changes pre- and post-treatment in the last 65 years. The target population was anorectic adults with chronic long-term illness (cancer, HIV, cystic fibrosis) or the elderly (ages over 65). Outcomes using pooled-weighted-standard-mean effect sizes were analyzed using a random effects model with Bayesian and frequentist methods. Meta-regressions with artificial neural nets were used to validate results and predict response to treatments. A total of 74 studies were included in the network meta-analysis out of the retrieved 340 articles, and 16,390 patients were analyzed in total. The random effects model calculated a pooled-weighted-effect size (p<0.0001) for olanzapine [0.87, confidence interval (CI) 95% (0.66-0.97)], for megestrol acetate high-dose [0.72, CI 95% (0.53-0.91)], for anamorelin [0.56, CI 95% (0.36-0.77)], for megestrol acetate low-dose [0.47, CI 95% (0.25-0.69)], for mirtazapine [0.42, CI 95% (0.13-0.72)], and for nutritional supplementation [0.45, CI 95% (0.29-0.61)]. Cannabinoids, cyproheptadine, other antidepressants, and steroids did not perform well. Between-study heterogeneity was tau-squared (τ²)=0.03. Subgroup analysis indicates that olanzapine is most effective for cancer patients, followed by megestrol acetate in high doses and anamorelin. Results were inconclusive for other patient groups. Olanzapine-induced weight gain is an adverse drug reaction that can be explained by pharmacogenomics affecting gut-microbiota dysbiosis. Compared to megestrol acetate and anamorelin, it has fewer side effects, improves sleep and mood, and has proven anti-nausea/anti-vomiting effects in chemotherapy. Furthermore, it inhibits some types of cancer cells and can be cytotoxic. Drug repositioning of olanzapine and anamorelin for cancer, elderly, HIV, and cystic fibrosis patients as orexigenic agents should be explored further. Appropriate nutritional supplementation should augment anorexia treatments.

Alnajar M, Darawad M, Khater W, et al. Exploring palliative care needs among patients with cancer and non-cancer serious chronic diseases: a comparison study. Am J Hosp Palliat Care 2025;42:20-31. DOI: https://doi.org/10.1177/10499091241235920

Ispoglou T, McCullough D, Windle A, et al. Addressing cancer anorexia-cachexia in older patients: potential therapeutic strategies and molecular pathways. Clin Nutr 2024;43:552-66. DOI: https://doi.org/10.1016/j.clnu.2024.01.009

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17-48. DOI: https://doi.org/10.3322/caac.21763

Galmiche M, Dechelotte P, Lambert G, Tavolacci MP. Prevalence of eating disorders over the 2000-2018 period: a systematic literature review. Am J Clin Nutr 2019;109:1402-13. DOI: https://doi.org/10.1093/ajcn/nqy342

Fielding RA, Landi F, Smoyer KE, et al. Association of anorexia/appetite loss with malnutrition and mortality in older populations: a systematic literature review. J Cachexia Sarcopenia Muscle 2023;14:706-29. DOI: https://doi.org/10.1002/jcsm.13186

Famularo P. Unintended weight loss in older adults: is there an indication for appetite stimulants? Caring for the Ages 2023;24:P6. DOI: https://doi.org/10.1016/j.carage.2023.08.008

Zupo R, Castellana F, Bortone I, et al. Nutritional domains in frailty tools: working towards an operational definition of nutritional frailty. Ageing Res Rev 2020;64:101148. DOI: https://doi.org/10.1016/j.arr.2020.101148

Dibello V, Zupo R, Sardone R, et al. Oral frailty and its determinants in older age: a systematic review. Lancet Healthy Longev 2021;2:e507-20. DOI: https://doi.org/10.1016/S2666-7568(21)00143-4

Lorenzo-Lopez L, Maseda A, de Labra C, et al. Nutritional determinants of frailty in older adults: a systematic review. BMC Geriatr 2017;17:108. DOI: https://doi.org/10.1186/s12877-017-0496-2

Taniguchi J, Mikura S, da Silva Lopes K. The efficacy and safety of anamorelin for patients with cancer-related anorexia/cachexia syndrome: a systematic review and meta-analysis. Sci Rep 2023;13:15257. DOI: https://doi.org/10.1038/s41598-023-42446-x

Lim YL, Teoh SE, Yaow CYL, et al. A systematic review and meta-analysis of the clinical use of megestrol acetate for cancer-related anorexia/cachexia. J Clin Med 2022;11:3756. DOI: https://doi.org/10.3390/jcm11133756

Hammond S, Erridge S, Mangal N, et al. The effect of cannabis-based medicine in the treatment of cachexia: a systematic review and meta-analysis. Cannabis Cannabinoid Res 2021;6:474-87. DOI: https://doi.org/10.1089/can.2021.0048

Ruiz-Garcia V, Lopez-Briz E, Carbonell-Sanchis R, et al. Megestrol acetate for cachexia-anorexia syndrome. A systematic review. J Cachexia Sarcopenia Muscle 2018;9:444-52. DOI: https://doi.org/10.1002/jcsm.12292

Karleen BTL. An investigation into the interaction of the microbiome-gut-brain axis with stress. 2023. PhD thesis, Massey University, Turitea, Manawatū, New Zealand. https://mro.massey.ac.nz/handle/10179/18307

Picca A, Calvani R, Coelho-Junior HJ, et al. Anorexia of aging: metabolic changes and biomarker discovery. Clin Interv Aging 2022;17:1761-7. DOI: https://doi.org/10.2147/CIA.S325008

Steiner L, Brunetti L, Roberts S, Ziegler J. A review of the efficacy of appetite stimulating medications in hospitalized adults. Nutr Clin Pract 2023;38:80-7. DOI: https://doi.org/10.1002/ncp.10839

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. DOI: https://doi.org/10.1136/bmj.n71

Borgo F, Garbossa S, Riva A, et al. Body mass index and sex affect diverse microbial niches within the gut. Front Microbiol 2018;9:213. DOI: https://doi.org/10.3389/fmicb.2018.00213

Jenkins DA, Hussein H, Martina R, et al. Methods for the inclusion of real-world evidence in network meta-analysis. BMC Med Res Methodol 2021;21:207. DOI: https://doi.org/10.1186/s12874-021-01399-3

Riley RD DS, Donegan S, et al. Using individual participant data to improve network meta-analysis projects. BMJ Evid Based Med 2023;28:197-203. DOI: https://doi.org/10.1136/bmjebm-2022-111931

Jiang L, Nie L, Yuan Y. Elastic priors to dynamically borrow information from historical data in clinical trials. Biometrics 2023;79:49-60. DOI: https://doi.org/10.1111/biom.13551

Nikolakopoulou A, Higgins JPT, Papakonstantinou T, et al. CINeMA: an approach for assessing confidence in the results of a network meta-analysis. PLoS Med 2020;17:e1003082. DOI: https://doi.org/10.1371/journal.pmed.1003082

Higgins JPT TJ, Chandler J, Cumpston M, et al. Cochrane handbook for systematic reviews of interventions version 6.5. Cochrane; 2024.

Cohen J. Statistical analysis for the behavioural sciences. Mahwah, NJ, USA: Lawrence Erlbaum Associates, Inc.; 1988.

Hedges LV, Olkin I. Statistical methods for meta-analysis. New York, NY, USA: Academic Press; 1985.

Gibbons RD, Hedeker DR, Davis JM. Estimation of effect size from a series of experiments involving paired comparisons. J Educ Stat 1993;18:271-9. DOI: https://doi.org/10.3102/10769986018003271

Borenstein M, Hedges LV, Higgins JPT, Rothstein H. Introduction to meta-analysis, 2nd edition. Hoboken, NJ, USA: John Wiley & Sons; 2021. DOI: https://doi.org/10.1002/9781119558378

Zhang J, Ko CW, Nie L, et al. Bayesian hierarchical methods for meta-analysis combining randomized-controlled and single-arm studies. Stat Methods Med Res 2019;28:1293-310. DOI: https://doi.org/10.1177/0962280218754928

Donegan S, Dias S, Welton NJ. Assessing the consistency assumptions underlying network meta-regression using aggregate data. Res Synth Methods 2019;10:207-24. DOI: https://doi.org/10.1002/jrsm.1327

Salanti G, Dias S, Welton NJ, et al. Evaluating novel agent effects in multiple-treatments meta-regression. Stat Med 2010;29:2369-83. DOI: https://doi.org/10.1002/sim.4001

Spiegelhalter DJ, Best NG, Carlin BP, Linde A. The deviance information criterion: 12 years on. J R Stat Soc Ser B Stat Methodol 2014;76:485-93. DOI: https://doi.org/10.1111/rssb.12062

Brooks SP, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 1998;7:434-55. DOI: https://doi.org/10.1080/10618600.1998.10474787

Gelman A, Carlin JB, Stern HS, et al. Bayesian data analysis, third edition. 2013. Available from: https://sites.stat.columbia.edu/gelman/book/BDA3.pdf. DOI: https://doi.org/10.1201/b16018

Miller PMABT. Foundations of agnostic statistics. Cambridge, UK: Cambridge University Press; 2019.

Wang Y, Lin L, Thompson CG, Chu H. A penalization approach to random-effects meta-analysis. Stat Med 2022;41:500-16. DOI: https://doi.org/10.1002/sim.9261

Krahn U, Binder H, Konig J. A graphical tool for locating inconsistency in network meta-analyses. BMC Med Res Methodol 2013;13:35. DOI: https://doi.org/10.1186/1471-2288-13-35

Efthimiou O, Debray TP, van Valkenhoef G, et al. GetReal in network meta-analysis: a review of the methodology. Res Synth Methods 2016;7:236-63. DOI: https://doi.org/10.1002/jrsm.1195

Veroniki AA, Tsokani S, White IR, et al. Prevalence of evidence of inconsistency and its association with network structural characteristics in 201 published networks of interventions. BMC Med Res Methodol 2021;21:224. DOI: https://doi.org/10.1186/s12874-021-01401-y

Pérez-Ortega J, Nely Almanza-Ortega N, Vega-Villalobos A, et al. The K-means algorithm evolution. In: Sud K, Erdogmus P, Kadry S, eds. Introduction to data science and machine learning. London, UK: Intechopen; 2020. DOI: https://doi.org/10.5772/intechopen.85447

Harrer M, Cuijpers P, Furukawa TA, Eber DD. Doing meta-analysis with R: a hands-on guide Boca Raton, FL, USA: CRC Press; 2022. DOI: https://doi.org/10.1201/9781003107347

Mulchandani M, Shetty N, Conrad A, et al. Treatment of eating disorders in older people: a systematic review. Syst Rev 2021;10:275. DOI: https://doi.org/10.1186/s13643-021-01823-1

McMaster CM, Fong M, Franklin J, Hart S. Dietetic intervention for adult outpatients with an eating disorder: a systematic review and assessment of evidence quality. Nutr Rev 2021;79:914-30. DOI: https://doi.org/10.1093/nutrit/nuaa105

De Deyn PP, Carrasco MM, Deberdt W, et al. Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 2004;19:115-26. DOI: https://doi.org/10.1002/gps.1032

Kinon BJ, Stauffer VL, McGuire HC, et al. The effects of antipsychotic drug treatment on prolactin concentrations in elderly patients. J Am Med Dir Assoc 2003;4:189-94. DOI: https://doi.org/10.1097/01.JAM.0000073959.30368.6B

Street JS, Clark WS, Kadam DL, et al. Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in nursing home patients with Alzheimer’s dementia. Int J Geriatr Psychiatry 2001;16:S62-70. DOI: https://doi.org/10.1002/1099-1166(200112)16:1+<::AID-GPS569>3.0.CO;2-J

Street JS, Clark WS, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry 2000;57:968-76. DOI: https://doi.org/10.1001/archpsyc.57.10.968

Borders JC, Blanke S, Johnson S, et al. Efficacy of mealtime interventions for malnutrition and oral intake in persons with dementia: a systematic review. Alzheimer Dis Assoc Disord 2020;34:366-79. DOI: https://doi.org/10.1097/WAD.0000000000000387

Moreira SC, Jansen AK, Silva FM. Dietary interventions and cognition of Alzheimer’s disease patients: a systematic review of randomized controlled trial. Dement Neuropsychol 2020;14:258-82. DOI: https://doi.org/10.1590/1980-57642020dn14-030008

McTavish D, Thornton J. Appetite stimulants for people with cystic fibrosis. Cochrane Database Syst Rev 2022;9:CD008190. DOI: https://doi.org/10.1002/14651858.CD008190.pub3

Epifanio M, Marostica PC, Mattiello R, et al. A randomized, double-blind, placebo-controlled trial of cyproheptadine for appetite stimulation in cystic fibrosis. J Pediatr 2012;88:155-60. DOI: https://doi.org/10.2223/JPED.2174

Eubanks V, Koppersmith N, Wooldridge N, et al. Effects of megestrol acetate on weight gain, body composition, and pulmonary function in patients with cystic fibrosis. J Pediatr 2002;140:439-44. DOI: https://doi.org/10.1067/mpd.2002.121936

Homnick DN, Marks JH, Hare KL, Bonnema SK. Long-term trial of cyproheptadine as an appetite stimulant in cystic fibrosis. Pediatr Pulmonol 2005;40:251-6. DOI: https://doi.org/10.1002/ppul.20265

Bilbao A, Spanagel R. Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med 2022;20:259. DOI: https://doi.org/10.1186/s12916-022-02459-1

Simon L, Baldwin C, Kalea AZ, Slee A. Cannabinoid interventions for improving cachexia outcomes in cancer: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2022;13:23-41. DOI: https://doi.org/10.1002/jcsm.12861

Kasvis P, Vigano M, Vigano A. Health-related quality of life across cancer cachexia stages. Ann Palliat Med 2019;8:33-42. DOI: https://doi.org/10.21037/apm.2018.08.04

Turcott JG, Del Rocio Guillen Nunez M, Flores-Estrada D, et al. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer 2018;26:3029-38.

Siddiqui J, Samuel SK, Hayward B, et al. HIV-associated wasting prevalence in the era of modern antiretroviral therapy. AIDS 2022;36:127-35. DOI: https://doi.org/10.1097/QAD.0000000000003096

Harrison ME, Norris ML, Robinson A, et al. Use of cyproheptadine to stimulate appetite and body weight gain: a systematic review. Appetite 2019;137:62-72. DOI: https://doi.org/10.1016/j.appet.2019.02.012

Turcott JG, Zatarain-Barron ZL, Cardenas Fernandez D, et al. Appetite stimulants for patients with cancer: current evidence for clinical practice. Nutr Rev 2022;80:857-73. DOI: https://doi.org/10.1093/nutrit/nuab045

SaeTeaw M, Subongkot S, Chaiyakunapruk N. Comparative efficacy and safety of pharmacologic interventions for cachexia: a systematic review and network meta-analysis. Ann Oncol 2017;28:x155-x. DOI: https://doi.org/10.1093/annonc/mdx676.001

Temel JS, Abernethy AP, Currow DC, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016;17:519-31. DOI: https://doi.org/10.1016/S1470-2045(15)00558-6

Currow D, Temel JS, Abernethy A, et al. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol 2017;28:1949-56. DOI: https://doi.org/10.1093/annonc/mdx192

Patadia P, Considine RV. Anamorelin: ghrelin receptor agonism as a potential intervention for osteosarcopenia. J Clin Endocrinol Metab 2024;109:e1804-5. DOI: https://doi.org/10.1210/clinem/dgae043

Leese PT, Trang JM, Blum RA, de Groot E. An open-label clinical trial of the effects of age and gender on the pharmacodynamics, pharmacokinetics and safety of the ghrelin receptor agonist anamorelin. Clin Pharmacol Drug Dev 2015;4:112-20. DOI: https://doi.org/10.1002/cpdd.175

Poon IO, Ajewole V, Braun UK. A review of olanzapine in the treatment of cancer anorexia-cachexia syndrome. Pharmacy 2024;12:34. DOI: https://doi.org/10.3390/pharmacy12010034

Roeland EJ, Bohlke K, Baracos VE, et al. Cancer cachexia: ASCO guideline rapid recommendation update. J Clin Oncol 2023;41:4178-9. DOI: https://doi.org/10.1200/JCO.23.01280

Okamoto H, Shono K, Nozaki-Taguchi N. Low-dose of olanzapine has ameliorating effects on cancer-related anorexia. Cancer Manag Res 2019;11:2233-9. DOI: https://doi.org/10.2147/CMAR.S191330

Singuluri SL, Srinivasan N, Goenka L, et al. 275MO Phase III double blind placebo-controlled study of olanzapine for chemotherapy related anorexia in patients with advanced gastric, hepatopancreaticobiliary and lung cancer. Ann Oncol 2022;33:S1540. DOI: https://doi.org/10.1016/j.annonc.2022.10.302

da Fonseca GWP, Sato R, de Nazare Nunes Alves MJ, von Haehling S. Current advancements in pharmacotherapy for cancer cachexia. Expert Opin Pharmacother 2023;24:629-39. DOI: https://doi.org/10.1080/14656566.2023.2194489

De Conno F, Martini C, Zecca E, et al. Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Eur J Cancer 1998;34:1705-9. DOI: https://doi.org/10.1016/S0959-8049(98)00219-6

Duan B, Zhang Y, Wang X, et al. Effect of megestrol acetate combined with oral nutrition supplement in malnourished lung cancer patients: a single-center prospective cohort study. Front Nutr 2021;8:654194. DOI: https://doi.org/10.3389/fnut.2021.654194

Fietkau R, Riepl M, Kettner H, et al. Supportive use of megestrol acetate in patients with head and neck cancer during radio(chemo)therapy. Eur J Cancer 1997;33:75-9. DOI: https://doi.org/10.1016/S0959-8049(96)00309-7

Ruiz Garcia V, Lopez-Briz E, Carbonell Sanchis R, et al. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013;2013:CD004310. DOI: https://doi.org/10.1002/14651858.CD004310.pub3

Takahashi S, Matsumoto K, Ohba K, et al. The Incidence and management of cancer-related anorexia during treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. Cancer Manag Res 2023;15:1033-46. DOI: https://doi.org/10.2147/CMAR.S417238

Turcott J, Guillen-Núñez MDR, Flores D, et al. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer. 2018 Sep;26(9):3029-3038. doi: 10.1007/s00520-018-4154-9. Epub 2018 Mar 17. PMID: 29550881. DOI: https://doi.org/10.1007/s00520-018-4154-9

Caldiroli A, La Tegola D, Affaticati LM, et al. Clinical and peripheral biomarkers in female patients affected by anorexia: does the neutrophil/lymphocyte ratio (NLR) affect severity? Nutrients 2023;15:1133. DOI: https://doi.org/10.3390/nu15051133

Mullins N, Kang J, Campos AI, et al. Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders, and known risk factors. Biol Psychiatry 2022;91:313-27. DOI: https://doi.org/10.1016/j.biopsych.2021.05.029

Singh S, Ricardo-Silgado ML, Bielinski SJ, Acosta A. Pharmacogenomics of medication-induced weight gain and antiobesity medications. Obesity 2021;29:265-73. DOI: https://doi.org/10.1002/oby.23068

Ter Hark SE, Jamain S, Schijven D, et al. A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort). J Psychopharmacol 2020;34:524-31. DOI: https://doi.org/10.1177/0269881120907972

Delacretaz A, Glatard A, Dubath C, et al. Psychotropic drug-induced genetic-epigenetic modulation of the CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients. Clin Epigenetics. 2019;11:198. DOI: https://doi.org/10.1186/s13148-019-0792-0

Jimeno N, Velasco-Gonzalez V, Fierro I, et al. Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study. Sci Rep 2021;11:15304. DOI: https://doi.org/10.1038/s41598-021-94700-9

Tsai SJ. Critical issues in BDNF Val66Met genetic studies of neuropsychiatric disorders. Front Mol Neurosci 2018;11:156. DOI: https://doi.org/10.3389/fnmol.2018.00156

Zubiaur P, Soria-Chacartegui P, Koller D, et al. Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers. Biomed Pharmacother 2021;133:111087. DOI: https://doi.org/10.1016/j.biopha.2020.111087

Anton-Paduraru DT, Trofin F, Nastase EV, et al. The role of the gut microbiota in anorexia nervosa in children and adults-systematic review. Int J Mol Sci 2023;25:41. DOI: https://doi.org/10.3390/ijms25010041

Garcia N, Gutierrez E. Anorexia nervosa and microbiota: systematic review and critical appraisal. Eat Weight Disord 2023;28:1. DOI: https://doi.org/10.1007/s40519-023-01529-4

Smitka K, Prochazkova P, Roubalova R, et al. Current aspects of the role of autoantibodies directed against appetite-regulating hormones and the gut microbiome in eating disorders. Front Endocrinol 2021;12:613983. DOI: https://doi.org/10.3389/fendo.2021.613983

Torices S, Daire L, Simon S, et al. The NLRP3 inflammasome and gut dysbiosis as a putative link between HIV-1 infection and ischemic stroke. Trends Neurosci 2023;46:682-93. DOI: https://doi.org/10.1016/j.tins.2023.05.009

Misera A, Loniewski I, Palma J, et al. Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review. Front Microbiol 2023;14:1125022. DOI: https://doi.org/10.3389/fmicb.2023.1125022

Zhu Z, Gu Y, Zeng C, et al. Olanzapine-induced lipid disturbances: a potential mechanism through the gut microbiota-brain axis. Front Pharmacol 2022;13:897926. DOI: https://doi.org/10.3389/fphar.2022.897926

Carbone EA, D’Amato P, Vicchio G, et al. A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders. Eur Psychiatry 2020;64:e2. DOI: https://doi.org/10.1192/j.eurpsy.2020.109

Persico M, Abbruzzese C, Matteoni S, et al. Tackling the behavior of cancer cells: molecular bases for repurposing antipsychotic drugs in the treatment of glioblastoma. Cells 2022;11:263. DOI: https://doi.org/10.3390/cells11020263

Lu J, Zhang X, Su K, et al. Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress. Cell Commun Signal 2024;22:375. DOI: https://doi.org/10.1186/s12964-024-01747-y

Sanomachi T, Suzuki S, Kuramoto K, et al. Olanzapine, an atypical antipsychotic, inhibits survivin expression and sensitizes cancer cells to chemotherapeutic agents. Anticancer Res 2017;37:6177-88. DOI: https://doi.org/10.21873/anticanres.12067

Vlachos N, Lampros M, Voulgaris S, Alexiou GA. Repurposing antipsychotics for cancer treatment. Biomedicines 2021;9:1785. DOI: https://doi.org/10.3390/biomedicines9121785