Control Strategies for Carcinogenic-Associated Helminthiases: An Integrated Overview

Abstract

Helminthiases are extremely prevalent in the developing world. In addition, the chronic infection with some parasitic worms are classified as carcinogenic. Therefore, it is utmost importance to understand the parasite-host interactions, the mechanisms underlay carcinogenesis and how they could be counteracted. This knowledge may ultimately guide novel control strategies that include chemotherapy-based approaches targeting these pathogens and associated pathologies caused by their infections. Little is known on how some helminthiases are associated with cancer; however, it has been hypothesized that chemical carcinogenesis may be involved in the process. Here, we summarize the current knowledge on chemical carcinogenesis associated with helminthiases, along with available therapeutic options and potential therapeutic alternatives including chemotherapy and/or immunotherapy. Ideally, the treatment of the carcinogenic helminthiases should target both the parasite and associated pathologies. The success of any chemotherapeutic regimen often depends on the host immune response during the infection and nutritional status among other factors. The close association between chemotherapy and cell-mediated immunity suggests that a dual therapeutic approach would be advantageous. In addition, there is a pressing need for complementary drugs that antagonize the carcinogenesis process associated with the helminth infections.

Keywords: antioxidants; carcinogenesis; chemotherapy; helminths; immunotherapy.

Figure 1

Immunohistochemistry of bladder mucosa evidencing p53 tissue deposition (black circles) and S. haematobium eggs (black arrows).

Figure 2

Schematic depiction of hypothesized carcinogenesis induced by urogenital schistosomiasis (UGS). Several risk factors may play a role in the onset of UGS-associated bladder cancer. Both parasite- and host-associated factors may be involved during carcinogenesis. Chronic inflammation, fibrosis and granulomas (black arrows) induced by the eggs of the parasite may have a role in carcinogenesis. Also, mitogens and reactive metabolites of schistosome origin (e.g., catechol estrogens) could interact with host DNA to form adducts and to induce apurinic sites. These could eventually lead to p53 mutations that consequently lost the ability to repair DNA. Therefore, the mutations may accumulate and ultimately underlie the development of UGS-associated squamous cell carcinoma. Co-factors, such as a tentative microbiota associated with the parasite (Formenti et al., 2020), host microbiota dysbiosis during the infection, and other host-associated factors such as the formation of ROS/RNS during chronic inflammation, and fibrosis, tobacco smoke, gender, age and impaired immune system, are known to influence the development of bladder cancer. Laboratory studies have suggested that the administration of antioxidants may counteract the interaction of reactive metabolites with host DNA, tentatively, preventing the development of pre- and carcinogenic lesions and may contribute to the amelioration of the pathogenesis associated to the UGS.