Table 1 Summary of the evidence of anti-neoplastic role of the anti-parasitic drugs: their current indications, cellular cytotoxic mechanisms of cancers, BBB penetration profile and radiosensitivity response
Drug Name | Indications | Mechanism of Action | Efficacy in Cancers | Efficacy in Brain Cancers | BBB Penetrability | Radiosensitivity | Source |
|---|---|---|---|---|---|---|---|
Atovaquone | FDA-labelled: • Pneumocystis Pneumonia Non-FDA labelled: • Malaria • Toxoplasma Encephalitis • Toxoplasmosis • Babesiosis | • Mitochondrial dysfunction and oxidative stress • Akt/AMPK/mTOR pathway Inhibitor • STAT3 Inhibitor | • Breast Cancer • Hypopharyngeal carcinoma • Colorectal Carcinoma • Lung Carcinoma • Cervical Cancer • Retinoblastoma • Renal Cell Carcinoma • Acute Myeloid Leukemia • Thyroid Carcinoma | • Glioblastoma | Yes | • Hypopharyngeal Carcinoma | |
Ivermectin | FDA-labelled: • Infection by Onchocerca volvulus • Intestinal strongyloidiasis • Pediculosis Capitis • Rosacea Non-FDA labelled: • Ascariasis • Infection by Loa loa • Cutaneous larva migrans • Enterobiasis • Infection by Wuchereria bancrofti • Infestation by Phthirus pubis • Mansonelliasis • Scabies | • Mitochondrial dysfunction and oxidative stress • Akt/mTOR pathway inhibitor • Induces cytostatic autophagy by targeting PAK1/Akt axis • Induces chloride dependent membrane hyperpolarization • WNT/TCF pathway inhibitor • Induces DNA fragmentation and chromatin condensation • Inhibition of ROS-TFE3-dependent autophagy and enhancing apoptosis | • Renal Cell Carcinoma • Chronic Myeloid Leukemia • Breast Cancer • Ovarian Cancer • Colon Cancer • Leukemia • Melanoma • Oesophageal squamous cell carcinoma • Cervical Cancer | • Glioblastoma • Neuroglioma | Limited (increases with increase in concentration) | ||
Mefloquine | FDA-labelled: • Malaria | • PI3K/Akt/mTOR inhibitor • Mitochondrial dysfunction and oxidative stress • Lysosomal disruption • Disrupts endolysosomal RAB5/7 • Targets B-catenin pathway • Inhibits NF-κB signaling • Induces autophagy and endoplasmic reticulum stress | • Prostate Cancer • Gastric Cancer • Cervical Cancer • Acute Myeloid Leukemia • Chronic Lymphocytic Leukemia • Colorectal cancer • Liver cancer • Breast Cancer | • Glioblastoma | Yes | ||
Proguanil | FDA-labelled: • Malaria, Plasmodium Falciparum Non-FDA labelled: • Malaria, Plasmodium Vivax | • Mitochondrial dysfunction and oxidative stress | • Colon Cancer • Bladder Cancer | Yes | [115] | ||
Quinacrine | Non-FDA labelled: • Malaria • Giardiasis • Tapeworm infection • Systemic Lupus erythematosus • Rheumatoid arthritis • Malignant pleural effusions • Prevention of recurrent pneumothorax • Female sterilization | • DNA intercalator, inhibits DNA repair pathways • FACT c-trapping • Induces apoptosis via TRAIL signaling, modulating topoisomerases, inhibiting NF-κB and inducing p53 • Arachidonic acid pathway inhibitor • Induces cytostatic autophagy and inhibits cytoprotective autophagy • Modulates cell cycle arrest | • Breast Cancer • Colon Carcinoma • Ovarian Cancer • Non-small cell lung cancer • Diffuse large B-cell lymphoma • Colorectal Cancer • Leukemia • Renal Cell Carcinoma • Melanoma • Gastric Cancer • Anaplastic Thyroid Cancer | • Glioblastoma | Yes |