TLDR Ivermectin is a anticancer ionophoric
Ivermectin, antiviral properties and COVID-19: a possible new
mechanism of action
https://link.springer.com/content/pdf/10.1007/s00210-020-01902-5.pdf
(This one is kinda cool, but what is important is that ivermectin is an ionophore and ionophores are anti cancer.)
Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers
https://www.mdpi.com/2072-6694/10/10/360/htm
Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers
https://doi.org/10.3390/cancers10100360
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Conclusions
The disruption of ion homeostasis important for proliferation and survival of cancer constitutes a potential target for chemotherapy. The ionophores SAL, NIG and OBT have shown important anticancer activities in in vitro and in vivo preclinical models of cancer as single agents as well as in combination with other anticancer drugs. More important, they also showed anticancer activity against putative cancer stem-like cells. The underlying reason some ionophores work against cancer stem cells and other ionophores do not is poorly understood but it is possible that other ionophore-independent activity target key processes associated with stemness, for instance, (i) SAL induces ER Ca2+ depletion up-regulating C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin [168]. SAL also inhibits K-ras [169], Notch [82] and Hedgehog signaling [170], (ii) NIG is also a potent modulator of the Wnt signaling pathway [6] and (iii) OBT targets cancer stem cells via disruption of BCL-2-dependent oxidative phosphorylation [14].
Except for OBT, these ionophores have not been translated into clinical trials. At present, the results of clinical trials with OBT as single agent or in combination with other anticancer drugs did not show a significant benefit. It is possible that the high toxicity of ionophores towards non-cancer cells may be limiting their clinical use. The selectivity towards non-cancer cells can be investigated by using non-cancer cell lines from the same organ. For instance, the Beas-2B cell line consists of epithelial cells that were isolated from normal human bronchial epithelium obtained from autopsy of non-cancerous individuals and is sometimes used to compare to lung cancer cells [171]. To overcome this limitation, future development in targeted drug delivery may help to improve the ability of these promising compounds. The use of different types SAL loaded nanoparticles alone or in combination with other drugs showed improved efficacy compared to SAL alone in a variety of cancer cell types (Table 3). Alternatively, SAL, NIG and OBT may serve as lead compounds to develop derivatives more selective towards non-cancer cells. In this context, several derivatives of OBT [172,173] and SAL [120,121,174,175,176,177,178,179] have shown anticancer effects. For instance, derivatives with chemical modification of the allylic C20 hydroxyl of SAL, located at the C-ring, enhanced the activity over 5-fold against breast cancer cells compared to the native structure [121]. Derivatives of OBT were also found to be more potent against PLC5 hepatocellular carcinoma cells than the original compound [173]. At present the biological effects and selectivity, in particular the ability to deplete chemoresistant cells such as cancer stem-like cells need to be further investigated in more advanced preclinical (animal) models. In summary, targeted delivery and development of more potent and selective synthetic derivatives of concerned ionophores can facilitate the translation into clinical applications for cancer treatment.