FOLATES ARE THE MOST COMMONLY USED DRUGS IN CANCER TREATMENT TODAY
Folates are essential for life and reduced folates are the natural source of vitamin B9 found in a variety of foods, most often, in leafy green vegetables, dried beans, and peas. They are critical for cell growth inside the human body.
Folates have also been used in pharmacology and there are two main uses for reduced folates in the oncology field:
As biochemical modulators, enhancing the cytotoxic activity of 5-FU, which is a widely used oncology therapy, especially for the treatment of colorectal cancer.
As antidotes (also known as “rescue therapy”) to folic acid antagonists, such as methotrexate. This use has been applied in the treatment of certain neoplastic diseases, such as osteosarcoma, as well as in psoriasis and rheumatoid arthritis.
All current folate-based therapies used in cancer treatment are based on prodrugs that need multiple activation steps into an active metabolite to exert their actions. Isofol has shown that a few genes determine cancer patients’ ability to activate these prodrugs. By purifying the key active metabolite of all the marketed folate-based prodrugs, Isofol has created a product that does not require metabolic activation to exert its action. Against this background, arfolitixorin may be beneficial regardless of the patient’s genetic ability to activate folates and thus holds the potential to replace the folates used in cancer treatment today.
Direct correlation between the expression level of specific genes and the level of response to leucovorin or levoleucovorin treatment has been demonstrated.
A positive correlation has been shown between expression level of folate-associated genes and the level of the active metabolite in tumour tissue after different doses of leucovorin.
Even if the amount of leucovorin given to patients is increased it does not result in higher concentrations of the active metabolite in the tumour tissue of all patients, although GGH and TS gene expression do increase in response to increasing leucovorin dosages.
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