Seeking to block the effect of a key nutrient essential for the survival of malignant cells but not for normal counterpart cells. Malignant cells die over a period of a few days, but normal counterpart cells survive for extended periods (several months). The dietary restriction of this key nutrient has shown clinical responses published in peer-reviewed SCI journal, but it is hard to implement. We now have a new molecular way to block the signal transduction of this key nutrient.
The lead is based on a discovery originally published in “Science”, recognized and scrutinized by peers multiple times, including support from NCI (RO1 type of Investigator Initiated Grants, and highly prestigious Research Career Development Award of KO4 type) and others.
An enzymatic application of the key finding of his discovery has been patented in both US and EU; and a direct therapeutic application of the key finding has been proven effective in a clinical phase I/II study published in peer-reviewed medical scientific literature. However this direct application is hard to implement clinically on routine basis, as it is hard for patients to comply.
Recently a Japanese academic group defined signal transduction, which can be harnessed to his key finding to make highly effective anti-cancer molecularly targeting drugs, analogous to EGFR/TKI technically but entirely different conceptually, therefore there is the clear molecular target for a new anti-cancer medicine.
Dr Park has designed the necessary logistical steps that would be required to progress the project, including which initial tumor model system to be used (secured an email confirmation from a responsible NIH/NCI investigator for the availability of this model system needed), subsequent leukemic cells from patients with leukemia to be studied (available from medical school hospitals of Dr. Park's prior affiliation), and clinical studies Phases I to III (Phases I and II per above medical school hospitals, and Phase III to SWOG with which Dr. Park had decades of affiliation).
This should lead to an entirely new class of anti-cancer blockbuster drugs, effective for malignancies refractory to other currently available drugs with low or no adverse reactions.
In Dr Park's own words:
“It is not an easy task to disclose additional scientific and technical details without exposing confidential information, but let me try.
“In essence, this is to block the effect of a targeted key nutrient, which is essential for the survival of malignant cells but not for normal counterpart cells for an extended time period. Malignant cells die in a few days without this key nutrient, but normal counterpart cells survive for an extended period of time perhaps several months without it.
“There have been two independent human experiments with healthy volunteers on the depletion of this targeted key nutrient by dietary restriction, and published respectively in New England Journal of Medicine and Lancet. The results demonstrated that nothing happens to these volunteers in the short term, but after 4 or 5 months there appear a few clinically non-significant skin changes. It is only after 7 or 8 months of the depleted diet that any clinically significant adverse signs to develop. Therefore there is a wide window of several months to kill malignant cells without hurting normal cells. In the experiment published in NEJM, the primary author was a surgeon who placed himself on the restricted diet.
“We have in vitro data involving malignant cells from some 500 patients. In almost 50% of patients this peculiar dependency on the key nutrient is demonstrated. At the same time none of the counterpart normal cells from 100 tested individuals were affected, suggesting that future treatments exploiting this approach are likely to cause fewer adverse reactions.
“Because of the innate properties of the targeted key nutrient, the usual animal efficacy experiments involving mouse or rat models are not possible. However we do have a human clinical phase I/II study, by dietary restriction of this key nutrient, demonstrating efficacy and published in a respected medical scientific SCI journal peer reviewed. It is not easy to impose a strict dietary restriction of this key nutrient, as it is hard for patients to comply with this restricted diet. However, we now have the way to block the effect of this key nutrient by blocking the signal transduction for this key nutrient, and therefore we may not need any dietary restriction.
“Some more about the findings on the signal transduction by the academic group is appropriate here. Basically, its enhancement has resulted in increased DNA synthesis and cell proliferation both in vitro and in vivo in rats (non-cancer system). Although the enhancement was their primary goal, but there was some blocking possible. Also, it should be easier to tone down or block a signal transduction than to enhance it. One precaution here is that there may be more than one signal transaction involved, and blocking one transduction may not be sufficient as alternative transductions may bypass it. Here, we have the excellent opportunity to develop anti-cancer medicines similar to Erlotinib or Geftinib, technically, but radically different conceptually potentially opening up an entirely new field in cancer therapy.
“Another potential approach is an enzymatic decomposition of the key nutrient with a highly potent oxidase enzyme available in the markets for in vitro use now. In fact, I had patents both in the US and EU for the use of this enzyme in the treatment of human malignancies. This can be analogous to Asparaginase which once was popular and is still being used in the treatment of childhood leukemia (of course, my key nutrient has nothing to do with Asparagine). There must be other avenues to block the effect of this key nutrient including a monoclonal antibody (--mab) approach, therefore the IP needs to be widely- encompassing covering the potentially a whole new concept/field as mentioned above.
“Because all these are created based on an entirely new concept, we can expect these new anti-cancer medicine(s) should find their indications for malignancies not amenable to other commercially-available medicines currently available. There should also be little or no adverse reactions as this approach is highly selective against malignant cells with normal counterpart cells unaffected”.