Statins are cholesterol-lowering drugs that some integrativein cancer care, a patient-centered approach combining the best of conventional care, self care, and evidence-informed complementary care in an integrated plan oncologists use off-label to improve survival, although statins can have serious side effects.

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This section does not replicate the other information on this topic but provides additional details or context most relevant to professionals.

Modes of action

Statins inhibit the production of mevalonate, which also reduces the production of several isoprenoids that are necessary for the function of small GTPase oncogenes such as RAS.1Abdullah MI, de Wolf E, Jawad MJ, Richardson A. The poor design of clinical trials of statins in oncology may explain their failure – Lessons for drug repurposing. Cancer Treatment Reviews. 2018 Sep;69:84-89; Shimoyama S. Statins are logical candidates for overcoming limitations of targeting therapies on malignancy: their potential application to gastrointestinal cancers. Cancer Chemotherapy and Pharmacology. 2011 Apr;67(4):729-39; Yu R, Longo J et al. Statin-induced cancer cell death can be mechanistically uncoupled from prenylation of RAS family proteins. Cancer Research. 2018 Mar 1;78(5):1347-1357.

“Comparative analyses of gene expression profiles in breast cancer cell lines showed significant upregulation of the mevalonate and proapoptotic pathways following atorvastatin treatment.”2Bjarnadottir O, Kimbung S et al. Global transcriptional changes following statin treatment in breast cancer. Clinical Cancer Research. 2015 Aug 1;21(15):3402-11. 

Simvastatin decreases viability significantly by the induction of apoptosis, which is probably initiated by the mitochondrial caspase 9.3Chapman-Shimshoni D, Yuklea M, Radnay J, Shapiro H, Lishner M. Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9. Experimental Hematology. 2003 Sep;31(9):779-83.

The antitumor activity of liposomal pravastatin seems to result primarily from a local inhibition of tumor inflammation and stimulation of antitumor immune response.4Coimbra M, Banciu M et al. Liposomal pravastatin inhibits tumor growth by targeting cancer-related inflammation. Journal of Controlled Release. 2010 Dec 20;148(3):303-10.

Statins act as DNMT inhibitors, demethylating the BMP2 promoter, activating BMP signaling, inducing differentiation of CRC cells, and reducing ‘stemness.'5Kodach LL, Jacobs RJ et al. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ‘stemness’ via the bone morphogenetic protein pathway. Gut. 2011 Nov;60(11):1544-53.

Many observational and preclinical studies point to anticancer characteristics of statins:

  • Inhibiting tumor growth
  • Promoting programmed cell death
  • Preventing the development of new blood vessels
  • Preventing metastasis

All these processes play an important role in cancer causation, leading to oncologists’ interest in the role of statins in cancer prevention and treatment.

Through 3-hydroxy-3-methylglutaryl coenzyme A inhibition, statins show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/β-catenin signaling cascades.6Ampuero J, Romero-Gomez M. Prevention of hepatocellular carcinoma by correction of metabolic abnormalities: role of statins and metformin. World Journal of Hepatology. 2015 May 18;7(8):1105-11.

Based on preclinical studies, researchers suggest that statins, through disturbing lipid metabolism, may influence pathways that signal cell growth and survival, thus leading to programmed cell death.7Apostolova SN, Toshkova RA, Momchilova AB, Tzoneva RD. Statins and alkylphospholipids as new anticancer agents targeting lipid metabolism. Anticancer Agents in Medicinald Chemistry. 2016;16(12):1512-1522.

The antineoplastic effect (inhibiting or preventing the growth and spread of tumors or malignant cells) of statins might also arise from a number of non-cholesterol-mediated mechanisms, such as immunoregulation, antioxidant activity and indirect anti-inflammatory properties.8Alfaqih MA, Allott EH, Hamilton RJ, Freeman MR, Freedland SJ. The current evidence on statin use and prostate cancer prevention: are we there yet? Nature Reviews. Urology. 2017 Feb;14(2):107-119.

The anticancer effect of statins is a much more complex phenomenon and not only a result of their cholesterol-lowering effect.9Stryjkowska-Góra A, Karczmarek-Borowska B, Góra T, Krawczak K. Statins and cancers. Contemporary Oncology (Pozn). 2015;19(3):167-75.

Only lipophilic statins are able to permeate the cell membrane and affect cellular functions. Their study demonstrated that all lipophilic statins tested (lovastatin, atorvastatin, fluvastatin, and simvastatin) but not a hydrophilic statin (pravastatin) significantly inhibited the cell proliferation of breast cancer cell lines.”10Yao H, He G et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017 Jan 3;8(1):1913-1924.

More on safety and precautions

Liver function test (LFT) monitoring is necessary. Physicians must check LFTs at baseline, approximately 12 weeks after starting statin therapy, and then at 12 months.

Statin disposition and adverse events are linked to several pharmacogenetic variants. Risk for statin-associated musculoskeletal symptoms (SAMS) and other serious statin side effects may be increased based on genetic variations that affect statin exposure systemically. Evidence supports pharmacogenetic testing to determine which statins would be the safest and most effective for the individual patient, thereby improving adherence to therapy as well as mitigating the need to discontinue the statin. For more information see The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms ›

Some preclinical evidence indicates that statins may induce resistance to chemotherapy.11Ahmadi Y, Karimian R, Panahi Y. Effects of statins on the chemoresistance—the antagonistic drug-drug interactions versus the anti-cancer effects. Biomedicine and Pharmacotherapy. 2018 Dec;108:1856-1865.

Notable preclinical evidence

Clinical evidence is summarized in How can statins help you? What the research says ›

Improving treatment outcomes

We present preclinical evidence for cancer types missing clinical evidence.

Thyroid cancer
  • The combination of paclitaxel and lovastatin did not enhance the treatment effect in anaplastic thyroid carcinoma cell lines.12Chung YS, Cho S et al. Is there a treatment advantage when paclitaxel and lovastatin are combined to dose anaplastic thyroid carcinoma cell lines? Thyroid. 2011 Jul;21(7):735-44.
  • Rosuvastatin induced autophagic changes in B-CPAP papillary thyroid cancer cells in lower doses and caused a shift from autophagy to apoptosis.13Zeybek ND, Gulcelik NE et al. Rosuvastatin induces apoptosis in cultured human papillary thyroid cancer cells. Journal of Endocrinology. 2011 Jul;210(1):105-15.

Body terrain

Microbiome

Mevastatin and other HMG-CoA reductase inhibitors may enhance the antiproliferative effect of butyrate in colon cancer cells.14Wächtershäuser A, Akoglu B, Stein J. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2. Carcinogenesis. 2001 Jul;22(7):1061-7.

Managing side effects and promoting wellness

Pravastatin pre-administration prevented the nephrotoxicity induced by cisplatin in mice.15An Y, Xin H, Yan W, Zhou X. Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice. Experimental and Toxicologic Pathology. 2011 Mar;63(3):215-9.

Helpful links for professionals

Wiggins BS, Saseen JJ et al; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology; Council on Hypertension; Council on Quality of Care and Outcomes Research; and Council on Functional Genomics and Translational Biology. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2016 Nov 22;134(21):e468-e495.

Yeganeh B, Wiechec E et al. Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease. Pharmacology & Therapeutics. 2014 Jul;143(1):87-110. 

Keep reading about statins

Authors

Nancy Hepp, MS

past Lead Researcher
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS past Lead Researcher

Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, MSN, RN, OCNS Senior Clinical Consultant

Reviewers

Dr. Fuller-Shavel is a GMC-registered integrative medicine doctor with degrees in medicine and natural sciences from the University of Cambridge. Dr. Fuller-Shavel is a fellow of the College of Medicine and the vice chair for BSIO (British Society for Integrative Oncology). Alongside her science and medical training, Dr. Fuller-Shavel holds multiple qualifications in nutrition, integrative medicine, health coaching, herbal medicine, yoga, mindfulness and other mind-body approaches.

Dr. Fuller-Shavel is the director of Synthesis Clinic, an award-winning multidisciplinary integrative medicine practice in Hampshire, UK, specializing in women’s health, gut health (microbiome and gut-brain axis) and mental health. She combines her clinical work in women’s health and supporting patients with breast and gynecological cancer with education and training for healthcare professionals and research in precision cancer medicine and precision nutrition.

Nina Fuller-Shavel, MB, BChir, MA Hons, FBANT, IFMCP, DipIM, PG Cert RYT300

Last update: January 21, 2025

Last full literature review: April 2024

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

Our staff have no financial conflicts of interest to declare. We receive no funds from any manufacturers or retailers gaining financial profit by promoting or discouraging therapies mentioned on this site.

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