The Essential Molecular Requirements for the Transformation of Normal Cells into Established Cancer Cells, with Implications for a Novel Anti-cancer Agent

Background: Normal adult mammalian cells can respond to oncogenic somatic mutations by committing suicide through a well-described, energy dependent process termed apoptosis. Cancer cells avoid oncogene promoted apoptosis. Oncogenic somatic mutations are widely acknowledged to be the cause of the relentless unconstrained cell proliferation which characterises cancer. But how does the normal cell with the very first oncogenic mutation survive to proliferate without undergoing apoptosis?

New Findings: The phenomena of malignant transformation by somatic mutation, apoptosis, aneuploidy, aerobic glycolysis and Cdk4 upregulation in carcinogenesis have each been extensively discussed separately in the literature but an overview explaining how they may be linked at the initiation of the cancer process has not previously proposed.

Conclusion: A hypothesis is presented to explain how in addition to the initial oncogenic mutation, the expression of certain key normal genes is, counter-intuitively, also required for successful malignant transformation from a normal cell to a cancer cell. The hypothesis provides an explanation for how the cyclic amphiphilic peptide HILR-056, derived from peptides with homology to a hexapeptide in the C-terminal region of Cdk4, kill cancer cells but not normal cell by necrosis rather than apoptosis.