Compositions and methods for the prevention of cancer in high risk patients
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Assignees
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Publication Number
US-8969304-B2
Publication Date
2015-03-03
Expiration Date
Abstract
This relates to the prevention of cancer initiation. More specifically, the invention provides compositions and methods useful for altering the genetic signature in breast tissue, said alteration being correlated with a reduced risk for the development of breast cancer.
Core Innovation
The invention relates to preventing the initiation of breast cancer in a subject by administering hCG-derived LH/CG-R-targeting oligopeptides selected from SEQ ID NOs: 1-4, including variants, and acceptable salts. The peptides are provided in prophylactically effective doses for repeated administrations to alter breast tissue responses associated with reduced cancer risk. The approach is described as creating a pregnancy-like “genomic signature” in breast tissue that is linked to protection against cancer initiation.
The described peptides are stated to bind the LH/CG receptor (LHCGR) and to mimic hCG effects in breast tissue. Treatment is associated with increased ductulogenesis and/or differentiation, decreased cell proliferation and invasiveness, and down-regulation of CXCR1 while up-regulating LHCGR expression. Additional associations described include apoptosis and effects on DNA repair and DNA synthesis depression.
Chromatin remodeling and epigenetic profiling in breast tissue are used to identify and assess the protective genomic signature before and after treatment. Preclinical and in vitro findings are discussed, including the DMBA induced mammary tumor model and cell-based assays with receptor and signaling readouts such as cAMP induction and receptor expression changes. The disclosed concept includes evaluating protective signatures using genomic profiling tools such as laser capture microdissection and microarrays, gene expression analysis including real-time RT-PCR, and genomic feature assessments including microRNAs.
Claims Coverage
The partial content includes two independent claims. The inventive features cover a prophylactic method to inhibit breast cancer initiation using repeated administration of specified hCG-derived LH/CG-R-targeting oligopeptides and a pharmaceutical composition comprising a specified high-identity peptide with a pharmaceutically acceptable carrier.
Inhibiting breast cancer initiation with repeated oligopeptide administrations
A method of inhibiting the initiation of breast cancer in a subject by providing the subject with repeated administrations of an oligopeptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4, variants thereof, and acceptable salts thereof, wherein each variant has at least 90% identity with SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 4, and wherein each repeated administration comprises a dose of at least 0.250 mg peptide/kg bodyweight of the subject.
Pharmaceutical composition of a high-identity peptide with a pharmaceutically acceptable carrier
A composition comprising a peptide having at least 90% identity with SEQ ID NO: 1 and a pharmaceutically acceptable carrier.
Across the independent claims, the core coverage is a prophylactic approach that inhibits breast cancer initiation through repeated administration of specified SEQ ID NO: 1/2/4-derived oligopeptides, including high-identity variants, at a minimum peptide dose, and a corresponding pharmaceutical composition comprising a high-identity SEQ ID NO: 1 peptide formulated with a pharmaceutically acceptable carrier.
Stated Advantages
Inhibiting the initiation of breast cancer in a subject.
Creating a pregnancy-like genomic signature in breast tissue associated with reduced cancer risk.
Documented Applications
Prevention of cancer initiation in breast cancer, including prevention in subjects such as BRCA1/BRCA2 mutation carriers, as further narrowed in dependent claim context.
Assessment of protective genomic changes in breast tissue before and after treatment using genomic profiling, biopsies, and related assays mentioned in the partial content.
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