High Neutrophil-to-Lymphocyte Ratio Facilitates Cancer Growth—Currently Marketed Drugs Tadalafil, Isotretinoin, Colchicine, and Omega-3 to Reduce It: The TICO Regimen

SIMPLE SUMMARY: Several elements that are composed of, or related to, neutrophils, have been shown to inhibit strong immune responses to cancer and promote cancers’ growth. This paper presents the collected data showing these elements and how their coordinated actions as an ensemble facilitate growth in the common cancers. The paper goes on to present a drug regimen, TICO, designed to reduce the cancer growth enhancing effects of the neutrophil related elements. TICO uses four already marketed, readily available generic drugs, repurposed to inhibit neutrophil centered growth facilitation of cancer. ABSTRACT: This paper presents remarkably uniform data showing that higher NLR is a robust prognostic indicator of shorter overall survival across the common metastatic cancers. Myeloid derived suppressor cells, the NLRP3 inflammasome, neutrophil extracellular traps, and absolute neutrophil count tend to all be directly related to the NLR. They, individually and as an ensemble, contribute to cancer growth and metastasis. The multidrug regimen presented in this paper, TICO, was designed to decrease the NLR with potential to also reduce the other neutrophil related elements favoring malignant growth. TICO is comprised of already marketed generic drugs: the phosphodiesterase 5 inhibitor tadalafil, used to treat inadequate erections; isotretinoin, the retinoid used for acne treatment; colchicine, a standard gout (podagra) treatment; and the common fish oil supplement omega-3 polyunsaturated fatty acids. These individually impose low side effect burdens. The drugs of TICO are old, cheap, well known, and available worldwide. They all have evidence of lowering the NLR or the growth contributing elements related to the NLR when clinically used in general medicine as reviewed in this paper.