Download Lancet_abstract 13.7 KB

In 2012 there were 11,957,599 advanced cancer cases in the US reported by CDC and the incidence has
been almost unchanged over the previous 8 years (482,000 cases in 2000 versus 456,000 cases in 2008).
There has been an annual percentage change of only (-0.6) between years 1999 to 2008 in cancer
incidence.
It is well described in the recent literature that epigenetic alterations are at least if not more important
than genetic defects for the development and progression of malignant diseases. In the therapeutic
field, transcriptional therapy is a very promising form of cancer treatment that is being extensively
evaluated. It is speculated that inhibitors of DNA methylation and histone deacetylases can reactivate
expression of tumor suppressor genes and induce histone hyperacetylation in the tumors of patients
with solid cancers after treatment with these agents. Hypermethylation and transcription silencing of
suppressor genes has been shown in 33% of breast cancers, 60% of prostate CA and 92% of colon CA.
Although the value of such combination therapy both in chemoprevention, as well as treatment in
patients with cancer is extremely important and can cause a significant shift in the current practice of
oncology and cancer prevention, unfortunately, the results in clinical studies have been poor as the
target histone hyperacetylation does not correlate with survival ( possibly due to P 16/21 resistance and
unselectiveness of the conventional therapies/targets).
Here this synergism is shown to be clinically relevant in a set of cases treated with a combination of
epigenetic modifiers, using off label and natural therapies in a protocol called Multi targeted epigenetic
therapy ( MTET), using non toxic natural substances currently tested in preclinical studies of cell cultures
with preliminary results confirming apoptosis. Clinical application of such method of treating cancer has
caused promising preliminary results. Here we present the summary of outcomes in thirty cases of
advanced cancer with three cases, described in detail, that were treated through this method. We
conclude that further research is warranted in a larger spectrum and clinical trial setting to evaluate the
efficacy of such method.