Abstract
The term “Achilles Heel” has often been used in relation to potentially vulnerable target molecules for anticancer drugs within cancer cells. Its generalized application to an increasing range of diverse possibilities, however, detracts from the uniquely valuable way it describes the wild-type aerobic glycolysis target which persists within the immortal cancer cell phenotype. Here it is proposed that the persistence of the PKM2 isoform of the normal non mutant pyruvate kinase gene which induces aerobic glycolysis in a cancer cell whose phenotype has otherwise been immortalized by oncogenic somatic mutation provides a close analogous comparison with the immortal body of Achilles and his mortal vulnerable heel. Exploitation of the mechanism believed to explain the way aerobic glycolysis helps avoid oncogene induced apoptosis has led to the development of ONKONEK, a first in class therapeutic agent employing the new therapeutic paradigm of selective cancer cell limotherapy (SCCL) which starves cancer cells rather than attacking their cell division and is not expected to be restricted by the limitations of current chemotherapy.
The new therapeutic paradigm of selective cancer cell limotherapy (SCCL) starves cancer and, in particular, down-regulates PKM2 activity during cytokinesis in mitosis addicted cancer cells. Selective cancer cell limotherapy, by sparing normal cells provides a potential global cancer treatment which could potentially be delivered repeatedly until every cancer cell is destroyed.
Keywords
Aerobic glycolysis, Cancer, CDK4, Limotherapy, PKM2