Fenbendazole, a benzimidazole, is an anthelminthic drug that has been used for the treatment of gastrointestinal nematodes in humans and animals. In preclinical studies, fenbendazole enhancing has also shown to be effective against cancer, especially neuroblastoma (NB). This study aimed to evaluate the efficacy of fenbendazole in enhancing the anti-tumor effect of standard chemotherapy drugs in patients with NB. Let’s look at various cases that show the effectiveness of the drug!

Antiparasitic drugs repositioned as Fenbendazole Enhancing anti-tumor agents

Repositioning is the process of discovering a new use for a drug or therapy that was previously used for an unrelated indication. It has been increasingly common in oncology to reposition antiparasitic drugs as anti-tumor agents. This review will discuss the history of this repurposing and its current status in cancer research.

Parasites are a common cause of morbidity in humans and other animals. Most human parasites are protozoa, which have complex life cycles that include stages that live within and outside the host. The latter stages are transmitted to new hosts via an intermediate vector. A single drug is effective against all parasite life cycle stages. Targeting multiple parasitic stages with a single drug has led to the repositioning of antiparasitic drugs as novel agents against cancer.

Progress on the Use of Macrolide Antiparasitic Drugs for Treating Cancer

The use of antiparasitic drugs for treating cancer has progressed rapidly in recent years. Source The first case report on using ivermectin (IVM) to treat metastatic colon cancer was published in 2004. Since then, several reports have been published showing that these drugs are effective against various solid tumors, including breast, prostate, and renal cancers.

Avermectins

The broad-spectrum antiparasitic drug ivermectin is effective in cancer patients with cutaneous metastases. In one case report, a patient with melanoma and multiple cutaneous metastases was treated with a single dose of ivermectin (200 microg/kg). The patient experienced complete regression of his cutaneous metastases within two weeks. This study proves that the macrolide class of antiparasitic drugs may be helpful as an adjunct treatment for cutaneous metastases.

Milbemycins

Milbemycin oxime (MBO) is an imidazole derivative with activity against nematodes, arthropods, and some fungi. Source MBO has been used to treat various diseases in livestock, including nematodes causing pinworm infection in sheep and cattle (Ostertagia spp., Cooperia spp.). Milbemycin oxime has also been used as an oral treatment for liver fluke disease caused by Fasciola hepatica in sheep and goats.

The antibiotic milbemycin has been used for decades to treat parasitic infections such as heartworm disease and echinococcosis. Milbemycin was found to have broad-spectrum activity against helminths, arthropods, and some protozoa. Recent research has identified a mechanism of action that may also be useful in treating cancer. Milbemycin inhibits lipid IIA biosynthesis in target cells, preventing the formation of the cell membrane phospholipid bilayer needed for normal cellular function. This inhibition leads to apoptosis or programmed cell death in cancer cells. The main targets for milbemycin are macrophages (immune cells) and endothelial cells (lining blood vessels).

Progress on the Use of Benzimidazole Antiparasitic Drugs for Treating Cancer

The benzimidazole antiparasitic drug albendazole is an anti-cancer agent that has been repositioned. The use of albendazole in cancer treatment was described in this case series. Fenbendazole Enhancing, a benzimidazole antiparasitic drug, is currently being investigated for its potential to reposition as a cancer therapeutic agent. As with other benzimidazoles, flubendazole has demonstrated significant preclinical efficacy against various cancers. In particular, flubendazole has shown significant anti-tumor effects in animal models of hematological malignancies, including lymphoma and leukemia. It has been proved to be effective through the following tests:

Albendazole

Albendazole is currently used as an antihelminthic agent and antiparasitic drug. It inhibits microtubule polymerization by binding to the β-tubulin subunit and preventing tubulin assembly into microtubules. Source This disrupts cell division, leading to the death of parasites in the gastrointestinal tract. The drug has also been shown to induce programmed cell death (apoptosis) in several tumor cell lines, including neuroblastoma, melanoma, colorectal cancer, breast cancer, and glioblastoma multiforme. It has been shown that albendazole inhibits angiogenesis by inhibiting NF-κB activation and reducing MMP-2 production. Additionally, albendazole was found to inhibit the proliferation of prostate cancer cells through inhibition of NF-κB activation. These studies suggest that albendazole might help treat neuroblastoma and prostate cancer.

Flubendazole

Flubendazole is a benzimidazole antiparasitic drug used to treat helminth infections. It has also been shown to be effective against some cancers. Source

In 2014, researchers from China reported that Fenbendazole Enhancing showed significant anti-tumor activity against human breast cancer cells in vitro and in vivo. The researchers found that flubendazole inhibited the growth of breast cancer cells through the induction of apoptosis (programmed cell death). They also found that flubendazole increased caspase-3 activity and reduced Bcl-2 expression in breast cancer cells, leading to apoptosis.

In 2015, researchers from Japan reported that flubendazole inhibited tumor growth in mice with glioblastoma multiforme (GBM). The researchers found that flubendazole induced apoptosis in GBM cells and inhibited angiogenesis by downregulating VEGF expression. They also found that flubendazole did not cause any significant adverse effects in mice treated with this drug for ten days at doses up to 50.

Progress on the Use of Quinoline Antiparasitic Drugs for Treating Cancer

Chloroquine (CQ) is a quinoline antiparasitic drug that has been used for decades for the treatment of malaria. It also has anti-inflammatory and anti-oxidant properties. CQ was shown to inhibit tumor growth in preclinical studies and phase I clinical trials in various types of cancer. Its effectiveness has been proved in the following ways:

Chloroquine

Chloroquine, a quinoline-based antimalarial drug, was also studied as a potential anticancer agent. Source In vitro studies show that chloroquine can inhibit angiogenesis and cell proliferation in various cancer cell lines. However, this drug has some side effects, including gastrointestinal disturbances, hypersensitivity reactions, and retinal damage.

Quinacrine

Quinacrine (QN) is another quinoline-based antimalarial drug studied as an anticancer agent. QN inhibits tumor growth in mouse xenograft models of liver and breast cancer. QN has mild side effects such as nausea and vomiting; however, it can cause severe toxicities such as hemolytic anemia, thrombocytopenia, and agranulocytosis.

Atovaquone

Atovaquone is an orally bioavailable quinoline antimalarial drug that effectively targets multiple cancers, including colon, lung, breast, prostate, leukemia, and thyroid cancers. Source Atovaquone targets mitochondrial cytochrome bc1 complex, required for ATP production in all eukaryotic cells. This inhibition of mitochondrial function leads to the activation of apoptosis pathways via the Bcl-2 family (such as Bax) and caspase activation. Atovaquone also inhibits angiogenesis by inhibiting vascular endothelial growth factor (VEGF) expression through downregulation of hypoxia-inducible factor 1α (HIF1α) expression.