ผลกระทบของภาวะอ้วนต่อโรคมะเร็ง: จากพยาธิกำเนิดสู่ความท้าทายทางเภสัชบำบัดและการจัดการน้ำหนักตัวจากการรักษา

Nutthada Areepium

doi:10.69598/tbps.21.2.153-164

Authors

Nutthada Areepium Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok

DOI:

https://doi.org/10.69598/tbps.21.2.153-164

Keywords:

obesity, cancer, pharmacokinetics, adverse drug reactions, weight management, pharmaceutical care

Abstract

Obesity is a critical risk factor influencing both cancer incidence and prognosis. This narrative review aims to provide readers with a comprehensive understanding of the obesity–cancer relationship across three key dimensions: (1) the pathogenic mechanisms by which obesity promotes tumor development and progression, (2) the impact of obesity on anticancer drug pharmacokinetics and the associated challenges in dose optimization, and (3) proactive pharmaceutical care strategies for obese cancer patients, including the management of treatment-induced weight gain. Pathogenetically, obesity promotes tumor progression through three principal mechanisms: chronic low-grade inflammation, hyperinsulinemia-driven dysregulation of the Insulin/IGF-1 signaling axis leading to aberrant cancer cell proliferation, and alterations in sex hormone metabolism that favor the growth of hormone-sensitive cancers. Regarding pharmacotherapy, obesity significantly alters the pharmacokinetics of anticancer agents, particularly by increasing the volume of distribution for lipophilic drugs and impairing drug clearance, thereby heightening the risk of severe adverse reactions including cardiotoxicity and peripheral neuropathy. Clinical evidence supports dosing based on actual body weight to prevent subtherapeutic exposure. Furthermore, this review highlights sarcopenic obesity, frequently exacerbated by corticosteroids and hormonal therapies, as a clinically underrecognized concern. Pharmacists play a pivotal role in proactive pharmaceutical care by optimizing dose individualization, monitoring drug safety, and managing metabolic complications to enhance therapeutic efficacy and patient quality of life.

References

World Health Organization. Obesity and overweight: fact sheet [Internet]. Geneva: WHO; 2021 [cited 2026 Mar 30]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

Aekplakorn W, Inthawong R, Kessomboon P, Sangthong R, Chariyalertsak S, Putwatana P, et al. Prevalence and trends of obesity and association with socioeconomic status in Thai adults: National health examination surveys, 1991–2009. J Obes. 2014;2014:410259.

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body fatness and cancer: Viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794-8.

Pischon T, Nimptsch K. Obesity and risk of cancer: an introductory overview. Recent Results Cancer Res. 2016;208:1-15.

Hanley MJ, Abernethy DR, Greenblatt DJ. The effect of obesity on drug pharmacokinetics in humans. Clin Pharmacokinet. 2010;49(2):71-87.

Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO Guideline update. J Clin Oncol. 2021;39(18):2037-48.

Vance V, Mourtzakis M, McCargar L, Hanning R. Weight gain in breast cancer survivors: Prevalence, pattern and health consequences. Obes Rev. 2011;12(4):282-94.

Demark-Wahnefried W, Rimer BK, Winer EP. Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol. 2001;19(23):2381-9.

World Health Organization. Regional Office for the Western Pacific. The Asia-Pacific perspective: Redefining obesity and its treatment. Sydney: Health Communications Australia; 2000.

Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study. Lancet Oncol. 2008;9(7):629-35.

National Cancer Institute. Obesity and cancer risk [Internet]. Bethesda (MD): National Cancer Institute; 2022 [cited 2024 Apr 1]. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk/obesity

Iyengar NM, Gucalp A, Dannenberg AJ, Hudis CA. Obesity and cancer mechanisms: Tumor microenvironment and inflammation. J Clin Oncol. 2016;34(35):4270-6.

Vansaun MN. Molecular pathways: Adiponectin and leptin signaling in cancer. Clin Cancer Res. 2013;19(8):1926-32.

Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8(12):915-28.

Cleary MP, Grossmann ME. Minireview: obesity and breast cancer: The estrogen connection. Endocrinology. 2009;150(6):2537-42.

Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy support for rapid tumor growth. Nat Med. 2011;17(11):1498-503.

Smit C, De Hoogd S, Brüggemann RJM, Knibbe CAJ. Obesity and drug pharmacology: A review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin Drug Metab Toxicol. 2018;14(3):275-85.

Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51(5):277-304.

Knibbe CAJ, Brill MJE, van Rongen A, Diepstraten J, van der Graaf PH, Danhof M. Drug disposition in obesity: Toward evidence-based dosing. Annu Rev Pharmacol Toxicol. 2015;55:149-67.

Guenancia C, Lefebvre A, Cardinale D, Yu AF, Ladoire S, Ghiringhelli F, et al. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2016;34(26):3157-65.

Greenlee H, Hershman DL, Shi Z, Kwan ML, Ergas IJ, Roh JM, et al. BMI, lifestyle factors and taxane-induced neuropathy in breast cancer patients: The Pathways study. J Natl Cancer Inst. 2016;109(2):djw206.

Pentassuglia L, Sawyer DB. The role of neuregulin-1beta/ErbB signaling in the heart. Exp Cell Res. 2009;315(4):627-37.

Crone SA, Zhao YY, Fan L, Gu Y, Minamisawa S, Liu Y, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med. 2002;8(5):459-65.

Timmins HC, Li T, Goldstein D, Trinh T, Mizrahi D, Harrison M, et al. The impact of obesity on neuropathy outcomes for paclitaxel- and oxaliplatin-treated cancer survivors. J Cancer Surviv. 2021;16:223-32.

Bilgic Gazioglu S, Akan G, Atalar F, Erten G. PAI-1 and TNF-α profiles of adipose tissue in obese cardiovascular disease patients. Int J Clin Exp Pathol. 2015;8(12):15919-25.

Frischmuth T, Hindberg K, Aukrust P, Ueland T, Braekkan SK, Hansen JB, et al. Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism. J Thromb Haemost. 2022;20(7):1618-26.

Barginear M, Dueck AC, Allred JB, Bunnell C, Cohen HJ, Freedman RA, et al. Age and the risk of paclitaxel-induced neuropathy in women with early-stage breast cancer (Alliance A151411): Results from 1,881 patients from Cancer and Leukemia Group B (CALGB) 40101. Oncologist. 2019;24(5):617-23.

Giorgi-Pierfranceschi M, López-Núñez JJ, Monreal M, Cattabiani C, Lodigiani C, Di Micco P, et al. Morbid obesity and mortality in patients with VTE: Findings from real-life clinical practice. Chest. 2020;157(6):1617-25.

Goodwin PJ, Ennis M, Pritchard KI, McCready D, Koo J, Sidlofsky S, et al. Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis. J Clin Oncol. 1999;17(1):120-9.

Nguyen PL, Alibhai SMH, Basaria S, D’Amico AV, Kantoff PW, Mucci L, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825-36.

Ribed A, Romero-Jiménez RM, Escudero-Vilaplana V, Iglesias-Peinado I, Herranz-Alonso A, Codina C, et al. Pharmaceutical care program for onco-hematologic outpatients: Safety, efficiency and patient satisfaction. Int J Clin Pharm. 2016;38(2):280-8.

Xiang HW, Shen YY, Wang JX, Zhao Y, Yi BW, Zhao N. Impact of pharmacist-led interventions on oncology drug therapy outcomes: A systematic review and meta-analysis. Int J Pharm Pract. 2026;34(2):117-29.