Question

War on Cancer

The underlying assumption of most approaches contained within the War On Cancer is that we can find one cure for all cancers. Consider just two types of cancer: basal cell carcinoma and colon cancer. These are both caused by a combination of what particular alleles of certain genes a person is born with, and mutations that accumulate due to environmental exposure and the process of aging. Some of the genes are shared, and some differ between the diseases. How likely do you think it is that there is a single approach that can either prevent or cure both of these? How likely do you think it is that there is a single approach that can cure or prevent many cancers?

Answer 1

Tumor suppressor (P53), a key component of a system maintaining the genetic stability of human somatic cells. It provides instructions for making a protein called tumor protein (p53) which suppresses tumor growth by regulating cell division (keeping proliferative cells in a controlled manner) in the human. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired, or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. Although, TP53 gene is permanently transcribed in all cells of the body and its product does not accumulate in the healthy cell due to its rapid degradation by the proteasome. The degradation is specifically regulated by specific E3 ubiquitin ligases, encoded by murine double minute 2 protein (Mdm2) or Hdm2 in human via multiple modifications such as phosphorylation, acetylation, sumoylation, methylation, etc. The modifications evolve in response to various signals and weaken the interaction of TP53 with ubiquitin ligases, hence suppressing TP53 degradation and increasing the TP53 pool in the cell. However, these modifications modulate the functional properties of TP53.

Thus, if we modulate the mutp53 to wild type p53 activity using novel inhibitors or block MDM2 protein expression or both. Then WT p53 activity arrest cell cycle and inhibit the tumor proliferation significantly. This therapy will control all type of cancer.