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Jessica Desamero, PhD
Parasites, such as flatworms and amoeba, are like alien invaders: they live on or inside a host organism to obtain food and can cause the host much harm. For instance, they can cause parasitic diseases with severe symptoms, some of which are fatal. Similarly, cancer cells are invasive in that they grow uncontrollably, forming tumors, which can disrupt the body’s functions, possibly leading to death. In addition, both parasites and cancer cells are able to survive and grow on their own, are resistant to cell death, and can evade the host immune system’s defense mechanisms. Because of their fundamental similarities, they can have a special relationship.
Of the three main classes of parasites that cause various parasitic diseases in humans, two are related to cancer: helminths (parasitic worms) and protozoa (single-celled eukaryotic organisms). More specifically, some species of helminths are highly carcinogenic and can cause cancer, both directly and indirectly via various mechanisms. In fact, the International Agency for Research on Cancer (IARC), an intergovernmental agency that forms part of the World Health Organization of the United Nations, has classified three parasitic worm species as Group 1 carcinogens (agents that are definitely carcinogenic to humans). As for parasitic protozoa, some species are carcinogenic and mainly cause cancer indirectly. Several others have both cancer-causing and anticancer properties and thus play a dual role in cancer development. Because of their anticancer properties, these protozoan parasites may even have possible chemotherapeutic use.
Parasites as potent carcinogens
Several helminths are especially known to be highly carcinogenic and significantly increase the risk of cancer. For example, the urinary blood fluke Schistosoma haematobium, which is found in the water of some countries in the Middle East, Africa, and Asia, causes the disease called schistosomiasis. Schistosomiasis has been strongly linked to bladder cancer, or more specifically, bladder squamous cell carcinoma (SCC). Adult worms can be found around the urinary bladder, and their interactions with the host strongly induces the initiation of cancer formation. In addition, the eggs they release tend to migrate to the bladder wall, leading to bloody urine and chronic inflammation, which ultimately increases the risk of tumor formation and SCC.
Causing cancer indirectly
While some parasites can directly and definitively cause cancer, others can indirectly stimulate cancer development by triggering various mechanisms. In one possible mechanism, parasitic infection-induced chronic inflammation activates signaling pathways that could cause mutations and/or activate oncogenes. In another mechanism, some flukes secrete metabolites and other products that may induce oxidative stress, facilitating DNA damage and in turn, mutations. Mutations sometimes lead to cancer when they change proteins in ways that turn cancer cells cancerous. Lastly, as parasites grow, develop, and move, they can physically damage host tissues and trigger constantly active wound healing. This leads to increased cell transformation and proliferation, and with too much overproliferation, tumors can tend to form.
Parasites as anticancer agents and potential targets for cancer immunotherapy
With these detrimental outcomes, there is a silver lining: parasites can be helpful in treating cancer. First, some drugs mainly used to treat parasitic infections also have secondary anti-cancer effects. For instance, the drug Suramin is mainly used to treat the protozoan parasitic disease African sleeping sickness but also acts against prostate cancer. Possible reasons behind this mutual action could be that parasites and cancer cells have similar targets and express similar antigens (foreign substances that can trigger an immune response in the body).
Because antigens derived from microorganisms are very immunogenic, or highly able to induce an immune response, parasite-derived antigens with some degree of common origin with cancer antigens are potential targets for cancer immunotherapy. Moreover, parasites may even be able to overcome the immunological tolerance of the tumor microenvironment that deems a problem for cancer antigens.
Previous studies have explored the anticancer effects of parasites in vitro. In various investigations, cancer cells were treated with certain parasite-derived products, which stopped cancer growth and induced cancer cell apoptosis. For example, Trypanosoma cruzi is a parasitic protozoan species found mainly in Latin America, and it causes Chagas disease. T. cruzi can indirectly induce cancer, but it also has a number of anticancer effects. In two previous studies, treatment of breast cancer cells with T. cruzi lysates (preparations containing products resulting from cell disintegration via rupturing) inhibited further cell growth, and treatment of melanoma cells with an important surface protein of T. cruzi called gp82 induced cell death and apoptosis. Moreover, it has been shown that parasite-derived product treatment does not affect normal cells, and antibodies produced in response to parasitic infection also react against cancer cells. For example, gp82 treatment induces death in melanoma cells but leaves normal skin cells unharmed, and antibodies developed from T. cruzi infection also react against human breast cancer cells. This cross-reactivity and selectivity for cancer cells makes parasites possible candidates for selective cancer therapy.
The anticancer effects of parasites have been studied in vivo as well. Investigations involved either A) immunizing normal mice with parasites or parasite-related substances, challenging them with cancer cells, and seeing if this treatment prevents tumors from starting to grow, or B) treating tumor-bearing mice with parasites or parasite-related substances and seeing if this treatment inhibits further tumor growth. Results of these in vivo studies correlate with the results of in vitro studies. For example, immunizing mice models with T. cruzi lysates inhibited melanoma growth, and immunizing mice with T. cruzi extracts led to protective immune responses against breast cancers. This provides further evidence of parasites as potentially effective cancer immunotherapy targets.
Lastly, there is evidence showing parasites as potential anticancer agents on a global human population scale. For example, with the malaria-causing parasite, according to a study involving data compilation and analysis on worldwide malaria incidence versus mortalities related to 30 types of cancer in 56 countries, malaria incidence was negatively correlated with cancer mortality, particularly for colorectum, colon, stomach, lung, and breast cancer.
Conclusion
Inherently, parasites in the body are already highly damaging because of the parasitic diseases they carry. What’s worse is that some species of parasites can significantly increase the risk of cancer. But the silver lining is that, surprisingly, some parasites also have anti-cancer effects. Parasites can even be potential targets for cancer immunotherapy. More future studies would be needed before there can be clinical application, but based on the studies done so far, parasites are promising chemotherapeutic candidates.
Edited by Susan Egbert
Image Citations:
Works Cited:
https://www.cdc.gov/parasites/about.html
Çelik F, Şimşek S. Parasite and Cancer Relationship. Turkiye Parazitol Derg. 2022 May 23;46(2):150-162. English. doi: 10.4274/tpd.galenos.2022.30974. PMID: 35604195.
van Tong H, Brindley PJ, Meyer CG, Velavan TP. Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine. 2017 Feb;15:12-23. doi: 10.1016/j.ebiom.2016.11.034. Epub 2016 Dec 2. PMID: 27956028; PMCID: PMC5233816.
Brindley PJ, da Costa JM, Sripa B. Why does infection with some helminths cause cancer? Trends Cancer. 2015 Nov 1;1(3):174-182. doi: 10.1016/j.trecan.2015.08.011. Epub 2015 Sep 12. PMID: 26618199; PMCID: PMC4657143.
Yousefi, M., Akbari, M., hadipour, M. et al. Parasites as potential targets for cancer immunotherapy. J Cancer Res Clin Oncol 149, 8027–8038 (2023). https://doi-org.ezproxy.gc.cuny.edu/10.1007/s00432-023-04694-2
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