Drug Repurposing for Colorectal Cancer: Redesigning a House Into a Bookstore

By Douglas Chung

What if there was a quicker and cheaper way to bring forth more treatment options for people with cancer? Researchers are trying to do just that by repurposing drugs used for other diseases to treat cancer.

The process of drug development is a costly and lengthy process. Candidate drugs must undergo multiple stages of research and evaluation before they meet the safety and therapeutic requirements to be routinely used in the clinic.

Similar to building a new house, the drug development process requires a novel structural design, construction, and passing of safety regulations. However, once the house is built, it can often be repurposed for different uses including a bookstore, restaurant or dance studio.

Similarly, some approved drugs could be repurposed to treat other diseases than what they were originally intended for. Drug repurposing has gained a lot of interest within the cancer field. The advantage of this approach is that the initial research on how the drug works in the body and its potential side effects have already been done. Drug repurposing dramatically reduces the cost and time it takes to introduce new therapies for cancer patients.

Cimetidine: A treatment for heartburn repurposed for cancer

Cimetidine is an anti-histamine drug used to treat heartburn and peptic ulcers. In 1988, researchers reported that patients with stomach cancer, who happened to be treated with cimetidine for heartburn, demonstrated tumour shrinkage and increased survival [1]. In the past decade, an abundance of animal and clinical trials have provided evidence suggesting that this drug may be a good potential therapy for cancer. But how does a heartburn medication work against cancer?

Cimetidine promotes immune cells to attack tumour

One of the ways cimetidine promotes tumour regression is by promoting immune cells to attack cancer cells. The cells of the immune system are the defenders of our body from not only foreign substances like bacteria and viruses, but also from our own cells that have gone awry. They are capable of recognizing cancerous cells, and subsequently coordinating an organized attack against the tumour.

The best way to describe the epic battle between the immune system and cancer, is to compare it to famous scene in Star Wars when the Death Star (tumour) was attacked by the Rebel Alliance’s X-wing Starfighters (immune cells). Tumours have defensive mechanisms (the Empire’s TIE fighters, or in this case myeloid-derived suppressor cells and regulatory T cells) to stop immune cells from attacking it. This allows the tumour to continue to grow without surveillance.

Several studies have shown that cimetidine targets and shuts down the suppressor cells (Empire TIE fighters) [2,3]. By shutting down suppressor cells, the immune cells are free to attack the tumour with the ultimate goal of destroying that Death Star.

Cimetidine in colorectal cancer

A number of clinical trials have shown promising results using cimetidine to treat colorectal cancer. In a 2002 trial, 64 colorectal cancer patients underwent surgery and were given 5-fluorouracil, a common chemotherapy given after surgery. [4]. Of these 64 patients, 34 patients also received daily doses of cimetidine for a year starting 2 weeks after surgery. Patients were followed for 10 years and those given cimetidine had a higher survival rate.

A recent review which analyzed results from 5 clinical trials, with a total of 421 patients with colorectal cancer (CRC), further confirmed the positive survival benefits of receiving this drug post-surgery [5].

Cimetidine has also shown promise in melanoma, gastric cancer, and renal cell carcinoma [6]. More clinical trials are ongoing to investigate if cimetidine may also provide benefits in other cancer types and whether this is due to the enhancement of the immune system. Time will tell whether this repurposed drug becomes a standard treatment option for colorectal cancer and other cancer types.

This article was written by Douglas Chung. Douglas is a research assistant working in Dr. Pamela Ohashi’s Lab at the Princess Margaret Cancer Centre where he studies how to use the immune system to fight cancer. To learn more about Douglas and his research check out our members page.

References:

  1. To̸nnesen H, Bulow S, Fischerman K, Hjortrup A, Pedersen V.M, Svendsen L, et al. Effect of cimetidine on survival after gastric cancer. The Lancet. 1988;332(8618):990-992.
  2. Zheng Y, Xu M, Li X, Jia J, Fan K, Lai G. Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells. Molecular Immunology. 2013;54(1):74-83.
  3. Zhang Y, Chen Z, Luo X, Wu B, Li B, Wang B. Cimetidine down-regulates stability of Foxp3 protein via Stub1 in Treg cells. Human Vaccines & Immunotherapeutics. 2016;12(10):2512-2518.
  4. Matsumoto S, Imaeda Y, Umemoto S, Kobayashi K, Suzuki H, Okamoto T. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. British Journal of Cancer. 2002;86(2):161-167.
  5. Deva S, Jameson M. Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer. [Internet]. 2012 [cited 8 February 2017]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007814.pub2/full
  6. Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme V.P. Repurposing drugs in oncology (ReDO)—Cimetidine as an anti-cancer agent. ecancermedicalscience. 2014;8.
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