Colorectal cancer (CRC) ranks as the third most prevalent cancer in the United States, with approximately 93,090 new cases annually. Nearly half of these cases involve mutations in the KRAS and BRAF genes, rendering the disease more aggressive and resistant to conventional treatments and chemotherapy.
While Vitamin C is generally thought to improve health due to its antioxidant properties, which prevents or delays some types of cell damage, a study spearheaded by Dr. Lewis Cantley from Weill Cornell Medicine in New York City uncovered an intriguing twist concerning CRC linked to KRAS and BRAF mutations. Contrary to the typical antioxidant effect, high doses of Vitamin C induced oxidation in these cancer cells, potentially offering a beneficial impact for patients.
Experiments on cell cultures and mice revealed that high doses of Vitamin C, equivalent to about 300 oranges, hindered the growth of colorectal tumors carrying KRAS and BRAF mutations. The hope now is that these findings might pave the way for novel treatments and crucial insights into identifying individuals who would derive the most benefit from such approaches.
Within oxygen-rich environments like human arteries, Vitamin C, or ascorbic acid, undergoes oxidation, transforming into dehydroascorbic acid (DHA). Scientists knew that a membrane protein called glucose transporter GLUT1 facilitated the entry of both glucose and DHA into cells, but what happens to DHA inside the cells remained a mystery.
The latest research reveals DHA's role as a Trojan horse, that once inside the cancer cells, natural antioxidants attempt to convert DHA back to ascorbic acid, depleting these antioxidants and ultimately leading the cell to perish due to oxidative stress.
Dr. Cantley highlights that while many normal cells express GLUT1, KRAS- and BRAF-mutant cancer cells exhibit significantly higher levels to sustain their high glucose uptake for survival and growth. These cancer cells produces more reactive oxygen species than normal cells, and because of this, they require more antioxidants in order to survive. This combination of characteristics makes these cancer cells particularly susceptible to the effects of DHA.
Further investigation is essential as Vitamin C impacts cellular functions in various ways, not solely as an antioxidant or pro-oxidant. The impact of high-dose vitamin C on normal and immune cells is still not known. Dr. Cantley emphasizes the necessity for understanding the tumor's dynamics before considering this therapy.
However, researchers remain optimistic that they now have a mechanistic rationale for exploring the therapeutic use of Vitamin C in treating KRAS- or BRAF-related CRC. They believe the study could lead to the development of new biomarkers to help physicians identify suitable candidates for this treatment.
Additionally, these insights could hold promise for other challenging cancers that express high levels of the GLUT1 transporter, such as renal cell carcinoma, bladder cancer, and pancreatic cancer. Intravenous injections are likely the preferred route, as oral doses lack efficient absorption in the intestine to achieve the necessary high serum concentration of vitamin C needed to cause toxicity to these cancer cells.
Recent human clinical trials testing intravenous Vitamin C infusions for toxicity have shown promising safety profiles, aligning with the same levels of serum achieved in this research.