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Current Approach by others:
• Current anti-cancer drugs aim at the disrupted genes that
immortalise the cancer cell.
• Despite the development of a number of drugs, no reliable
general treatment for cancer is yet available.
TheRyte Approach:
• In normal cells the CDK (Cyclin Dependent Kinase) genes have a
well established “kinase” role causing cells signals for the
different phases of cell life activity.
• CDK4 is known to have a critical role in cancer, for example
mice cannot get cancer if CDK4 is knocked out. The role of CDK4 is
paradoxical in the cancer cell because despite its upregulation,
CDK4 kinase inhibitors have proved surprisingly ineffective in
attempts to cure cancer.
• After years of exploration of the relationships between the
expression of key cell cycle proteins in many different types of
cancer cells, and many different types of normal cells, TheRyte has
made the dramatic discovery of a totally unexpected 1:1 relationship
(p<0.001) between the level of expression of CDK4 and the level
of expression of CDK1 in cancer cells. This relationship has been
found consistently by TheRyte in different types of cancer, but it
does not exist in normal cells. This suggests to TheRyte some
“critical” relationship and function in cancer generally of the
“normal genes” CDK1 and CDK4, which they do not have in normal
cells.
• In view of these results, the known importance of CDK4 in
cancer, and the apparent irrelevance of kinase activity to this,
TheRyte has undertaken structural studies of CDK4 to look for
functionality in the non-kinase region of CDK4.
• This structural study has found an area of CDK4, in the
non-kinase region, which is very unusual in that it has a strongly
hydrophobic region on the outside of the structure. The outside
structure of a protein is normally hydrophilic.
• Using its findings about the relationship between CDK4 and CDK1
in cancer, TheRyte has postulated that this hydrophobic region of
CDK4 may interact with CDK1 in some unknown way which is important
in cancer cells, but not in normal cells.
• TheRyte has set out to test this theory by devising peptides
which mimic the hydrophobic region of CDK4. If these peptides were
to interact with CDK1, thus competitively displacing the CDK4
proteins, the apparently critical 1:1 ratio of CDK4 and CDK1 in
cancer would be disrupted by the presence of these peptides.
• These tests have been dramatically successful, see above. The
“mimetic” peptides cause cancer cells to die, but normal cells do
not die. As a control, similar peptides not with the sequence to
mimic the hydrophobic region of CDK4 do not kill cancer cells, or
normal cells.
• TheRyte’s has patent applications covering the critical normal
gene concept and the anti-cancer “CDK hydrophobic region
mimetic”peptide lead compounds.
• It is noted that the dramatic total death of the cancer cells
in the presence of the mimetic peptides takes place over a period of
weeks. This is not the cytotoxic mode of action of conventional
cancer chemotherapy. Instead it may be somehow the reintroduction of
senescence in cancer cells. However the theory is for exploration
later.
• In summary: TheRyte’s mimetic peptides kill cancer cells, do
not kill normal cells, and offer the pharmaceutical industry a
completely new lead to the general treatment of cancer.
• TheRyte is in discussion with potential pharmaceutical industry
partners to develop this lead into drug candidates, and so to
realise the potentially enormous clinical and financial implications
of this breakthrough.
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