USE OF FATOSTATIN FOR TREATING CANCER HAVING A p53 MUTATION
First Claim
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1. A method comprising:
- (a) identifying a subject having cancer, precancerous cells, or a benign tumor that has a mutated p53 gene or that expresses a mutant p53 protein or an mRNA encoding a mutant p53 protein; and
(b) administering to the subject a therapeutically effective amount of an SREBP cleavage activating protein inhibitor, in an amount that reduces or eliminates the cancer, the precancerous cells, or the benign tumor.
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Abstract
Fatostatin, a recently described inhibitor of SREBP activation, significantly reduces the level of mutant p53 binding to the HMG-CoA reductase gene promoter. Further, fatostatin treatment had a dramatic effect on normalizing the abnormal 3D morphology of 3 strains of breast cancer cells: MDA-468 cells, MDA-231 cells, and SKBR3 cells. The results show a functional interaction with SREBPs as being critical for mutant p53-mediated upregulation of the mevalonate pathway genes. At a clinical level, inhibition of the mevalonate pathway, either alone or in combination with other therapies, offers a novel, safe and much needed therapeutic option for tumors bearing mutant p53.
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Citations
24 Claims
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1. A method comprising:
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(a) identifying a subject having cancer, precancerous cells, or a benign tumor that has a mutated p53 gene or that expresses a mutant p53 protein or an mRNA encoding a mutant p53 protein; and (b) administering to the subject a therapeutically effective amount of an SREBP cleavage activating protein inhibitor, in an amount that reduces or eliminates the cancer, the precancerous cells, or the benign tumor. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24)
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13. A method for determining if cancer or precancerous lesions or benign tumors in a subject will be responsive to treatment with a SREBP cleavage activating protein inhibitor, comprising:
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(a) obtaining a biological sample of cells from the cancer, the precancerous lesions or the benign tumors from the subject; (b) assaying the cells in the sample for the presence of a mutated p53 gene or expression of a mutant form of p53 protein or a biologically active fragment thereof or an mRNA encoding the mutant form of p53 protein, and; (c) if the mutated p53 gene or the mutant form of the p53 protein or the mRNA encoding the mutant form of p53 protein is detected in the cells, then determining that the cancer, the precancerous lesions, the benign tumors will respond to treatment with the inhibitor.
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- 14. A method for preventing recurrence of cancer, precancerous lesions or a benign tumor having a mutated p53 gene or expressing a mutant form of p53 protein or a biologically active fragment thereof or an mRNA encoding the mutant form of p53 protein in a subject, comprising administering to the subject a prophylactically effective amount of an SREBP cleavage activating protein inhibitor.
- 15. A method of preventing cancer in a subject at high risk of developing a form of cancer that expresses a mutant p53 protein or a p53 gene mutation or an mRNA encoding a mutant form of p53 protein, comprising administering to the subject an SREBP cleavage activating protein inhibitor in a prophylactically effective amount.
- 18. A pharmaceutical composition comprising therapeutically effective amounts of fatostatin or an analogue thereof in a range of from about 0.1 mg to about 150 mg.
- 20. A pharmaceutical composition comprising therapeutically effective amounts of fatostatin or an analogue thereof in combination with one or more statins.
Specification