SYSTEMS AND METHODS FOR TREATING PATIENTS HAVING A GENETIC PREDISPOSITION TO DEVELOP PROSTATE CANCER

摘要

Systems and methods for mitigating prostate cancer development are provided. Peripheral blood cells may be evaluated for the presence or quantity of gamma-H2AX foci, and/or for gene alterations encoding a protein with impaired or lack of function, for example, because the encoded protein is truncated, and correlating with prostate cancer development. Such nucleic acids may encode proteins from or peripheral to the DNA damage repair pathway and/or androgen receptor signaling pathway, or that are otherwise correlated with prostate cancer development. Such genes include one or more of AKR1C1, PALB2, APTX, BLM, BRCA1, CTBP1, DDB2, FANCA, FANCL, MBD5, MSH3, NEIL3, RAD51D, RAD54L2, SP1, TP53BP1, UBE2D3, UBE2V2, NRIP1, EFCAB6, CRISP3, PAPSS2, ATP6V0A2, ALG13, MGAT2, B3GAT3, DOLK, FLT3, ASXL1, KDR, or NOTCH2.

主权项

1. A method for reducing the risk of developing prostate cancer in a human subject, comprising,
(a) isolating peripheral blood lymphocytes from a human subject and treating at least a portion of the isolated lymphocytes with a low dose of an agent or radiation that induces double stranded breaks in DNA; (b) determining whether the peripheral blood lymphocytes treated with the low dose of the agent or radiation have elevated levels of gamma-H2AX foci; (c) determining whether one or more genes encoding a protein from one or more of a DNA damage repair pathway, an androgen receptor signaling pathway, a protein that is peripheral to a DNA damage repair pathway or an androgen receptor signaling pathway, or that is associated with prostate cancer development obtained from the peripheral blood lymphocytes comprise one or more alterations that result in a protein with impaired functionality or substantially no functionality following expression of the protein; (d) optionally, determining whether the subject has prostate cancer; and (e) if the peripheral blood lymphocytes have elevated levels of gamma H2AX-foci and also have one or more of said genes comprising one or more alterations that result in a protein with impaired functionality or no functionality following expression of the protein, treating the subject with a treatment regimen capable of inhibiting the onset of prostate cancer derived from impaired DNA damage repair or of prostate cancer derived from impaired androgen signaling, and also with an enhanced regimen for monitoring prostate cancer development; or (f) if the peripheral blood lymphocytes have elevated levels of gamma H2AX-foci and also have one or more of said genes comprising one or more alterations that result in a protein with impaired functionality or no functionality following expression of the protein, and the subject has prostate cancer, treating the subject with one or more of a radical prostatectomy, a DNA-damaging therapy, or an androgen deprivation therapy.