Targeting gene amplification in cancer using triplex formation as a therapeutic strategy
AssigneeYale University
InventorFaye A. Rogers
Life of this patent
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Abstract
Disclosed herein are methods and agents for the treatment of cancer using p53-independent apoptosis to reduce the number of p53-depleted or p53-mutated cancer cells that have amplified HER2 gene. Also disclosed herein are methods and agents for the treatment of HER2-positive cancer in individuals with Li-Fraumeni Syndrome.
Claims68
A method of reducing, in a population of cells, the number of p53-depleted cancer cells in which a HER2 gene is amplified, the method comprising contacting p53-depleted cancer cells with triplex forming oligonucleotides (TFOs) targeted to a polypurine target site in the amplified-HER2 gene, under conditions under which the TFOs enter the p53-depleted cancer cells in sufficient quantity to induce apoptosis.
A method of reducing, in a population of cells, the number of p53-mutated cancer cells in which a HER2 gene is amplified, the method comprising contacting p53-mutated cancer cells with triplex forming oligonucleotides (TFOs) targeted to a polypurine site in the amplified-HER2 gene, under conditions under which the TFOs enter the p53-mutated cancer cells in sufficient quantity to induce apoptosis.
A method of treating cancer in an individual with Li-Fraumeni syndrome, the method comprising administering to the individual TFOs targeted to a polypurine target site in an amplified-HER2 gene, under conditions under which the TFOs enter p53-depleted cancer cells in sufficient quantity to induce apoptosis.
A method of administering TFOs for the treatment of cancer, the method comprising:
- (i) preparing a mixture of TFOs targeted to a polypurine target site in an amplified-HER2 gene;
- and
- (ii) administering the mixture of TFOs to an individual, in sufficient quantity to induce p53-independent apoptosis.
A composition, comprising:
- (i) TFOs targeted to a polypurine target site in an amplified-HER2 gene in sufficient quantity to induce p53-independent apoptosis in a p53-depleted cancer cell or a p53-mutated cancer cell;
- and
- (ii) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.