Cancer and parasitic infections: similarities and opportunities for the development of new control tools

Guilherme Oliveira
2014 Revista da Sociedade Brasileira de Medicina Tropical  
Lifestyle similarities between parasites and cancer have inspired parasitologists to use approaches analogous to those used in oncology and to explore the interface between these fields. The similarities have not escaped the notice of oncologists. Cancer may be thought of as a developing species that behaves in a manner akin to parasites 1 . Both are autonomous and not subjected to regular signaling mechanisms, although they make use of signals and resources for their own benefit. In
more » ... efit. In parasitology, research approaches inspired or enabled by cancer research have been used in the design of new antiparasitic drugs. For example, in schistosomiasis, imatinib, a drug used to treat chronic myelogenous leukemia (CML), has been found to produce a substantial effect on parasite physiology in vitro 2 . Examples of the use of kinases as drug targets can also be found in the literature for malaria and leishmaniasis, among others. Parasitic kinomes are also of interest, as kinases are key transducers of environmental signals and trigger physiological adaptations in the parasite. As both parasites and cancer capture environmental signals to modulate adaptations, the study of kinases is relevant for our understanding of host parasite/cancer interactions. Histonemodifying enzymes (HMEs) have also been intensively studied for drug development in cancer and parasitic diseases 3-5 . HMEs regulate epigenetic modifications of chromatin (reviewed 6 ). Epigenetic modifications mediate sequence-independent transcriptional regulation. Such modifications include DNA methylation or the alteration of histone proteins in a particular region. Histone modifications such as methylation or acetylation alter heterochromatin status, thereby regulating genes in the region. HMEs, specifically histone deacetylases (HDACs), are good antiparasitic targets; the drug suberanilohydroxamic acid (SAHA) inhibits parasite enzymatic activity. Active compounds have been developed to target the histone deacetylases of Plasmodium sp., Schistosoma mansoni, and other species 7,8 . A compound named SB939, a pan-HDAC inhibitor acting on class I, II, and IV HDACs, was found to inhibit asexual growth of Plasmodium in human erythrocytes and exoerythrocytic-stage parasites in human hepatocytes 7 . A structure-based approach was used to develop several small molecule inhibitors of the S. mansoni enzyme smHDA8 8 (Figure 1) , thus reducing parasite survival. Recently, a consortium was established to develop
doi:10.1590/0037-8682-0013-2014 pmid:24603730 fatcat:xpqlo63zvfa53bkorisdjcdnja