Does Tacrolimus Cause Cancer?

Check out this answer from Consensus:

The relationship between tacrolimus and cancer is complex and appears to be influenced by factors such as dosage, duration of exposure, and patient demographics. While some studies indicate an increased risk of malignancy with tacrolimus use, others suggest potential protective effects against specific cancers. Therefore, careful monitoring and individualized risk assessment are essential when using tacrolimus, particularly in long-term treatments.

Tacrolimus, a potent immunosuppressive agent, is widely used in organ transplantation to prevent rejection and in the treatment of various immune-mediated diseases. Despite its efficacy, concerns have been raised about its potential carcinogenic effects. This article aims to explore the relationship between tacrolimus use and cancer incidence, drawing on evidence from multiple research studies.

Evidence from Liver Transplantation Studies

Several studies have investigated the link between tacrolimus and cancer in liver transplant recipients. A multicenter case-control study involving 2,495 liver transplant patients found that increased cumulative exposure to tacrolimus was a significant predictor of post-transplant malignancy, even after controlling for clinical features and baseline hepatocellular carcinoma (HCC)1. Similarly, a prospective single-center study reported that higher mean blood concentrations of tacrolimus during the first year post-transplant were associated with a higher incidence of de novo solid cancers3. Another study from the Munich Transplant Centre also identified tacrolimus-based immunosuppression as a significant risk factor for de novo malignancies, particularly in older male patients8.

Impact on Specific Cancer Types

The risk of specific cancer types has also been examined. A cohort study comparing tacrolimus with cyclosporine in kidney transplant recipients found no significant difference in overall malignancy risk between the two drugs9. However, another study highlighted that tacrolimus enhances transforming growth factor-beta1 (TGF-β1) expression, which may promote tumor progression6. Additionally, a study on topical tacrolimus use in atopic dermatitis patients found an increased risk of lymphoma, although the absolute risk was small4.

Contradictory Findings

Interestingly, some studies have reported protective effects of tacrolimus against certain cancers. For instance, a study on oral carcinogenesis found that tacrolimus inhibited cancer formation and cell proliferation in an oral squamous cell carcinoma model2. Furthermore, a long-term safety study in children using topical tacrolimus for atopic dermatitis found no evidence of increased cancer incidence10.

Does Tacrolimus cause cancer?

S M Flechner has answered Unlikely

An expert from Cleveland Clinic in Urology

The answer to this question is somewhat nuanced and depends on the word “cause.” Tacrolimus was approved by the FDA over 20 years ago to prevent organ transplant rejection. Several hundred thousand people around the world have been given this drug, and there is no widespread known direct link to a particular cancer. However, the drug is given (either orally, iv, or topically) for immunosuppression, to block the immune response. It has distinct effects on immune active cells (T cells) that not only block rejection but can impair immune responses to infections and cancers. As an example, many cancers are induced by viruses, and since tacrolimus can impair the removal of viruses, such virally induced cancers can flourish (lymphoma, cervical cancer, Kaposi sarcoma, skin cancers, etc.). One can see this association with almost every form of immunosuppression to various degrees. That is why treated patients should undergo continuous screening and monitoring for such cancers. More subtle direct links to cancer at a sub cellular level may emerge in the future as more patients are studied.

Does Tacrolimus cause cancer?

Martin R First has answered Unlikely

An expert from Northwestern University School of Medicine in Internal Medicine, Medical Biotechnology

Transplantation is a life-saving therapy for patients with end-stage organ disease. However, the drugs administered to suppress the immune system and prevent rejection, also puts recipients at an increased risk for viral and other opportunistic infection and the development of post-transplant malignancy. As a result of chronic immunosuppression the risk of cancer that is 2-4 times higher in transplant recipients than the risk seen in the general population. Transplant recipients are at increased risk for a large number of different cancers. Some of these cancers can be caused by infectious agents, whereas others are not. The most common cancers among transplant recipients are basal and squamous cell carcinomas of the skin, non-Hodgkin’s lymphoma (NHL) and cancers of the lung, kidney, and liver. NHL can be caused by Epstein-Barr virus (EBV) infection, liver cancer by chronic infection with the hepatitis B (HBV) and hepatitis C (HCV) viruses, and Kaposi’s sarcoma is associated with infection by human herpesvirus-8 (HHV-8). Skin, lung and kidney cancers are not generally thought to be associated with infection. The effects of individual immunosuppressive drugs on cancer risk remains controversial. An increased risk of cancer in transplant recipients was first described in the 1960s in the era of azathioprine and prednisone. The incidence has increased progressively with the development of more potent immunosuppressive agents, namely anti-thymocyte globulin, cyclosporine, tacrolimus and mycophenolate mofetil. On the other hand, the mTOR inhibitors, sirolimus and everolimus, have been reported to be protective against certain post-transplant cancers. On balance, it would appear that no individual agent is responsible for the increased rate of malignancy seen after solid organ transplantation; rather it is the net state of immunosuppression induced by a combination of immunosuppressive drugs that determines the outcome. In spite of the elevated cancer risk in transplant recipients, the benefits of organ transplantation for people with end-stage organ disease far outweigh this risk.