Use of markers including filamin A in the diagnosis and treatment of prostate cancer
Inventors
Narain, Niven Rajin • VISHNUDAS, VIVEK K. • Sarangarajan, Rangaprasad • Akmaev, Viatcheslav R.
Assignees
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Publication Number
US-10539566-B2
Publication Date
2020-01-21
Expiration Date
Abstract
Methods for diagnosing the presence of prostate cancer in a subject are provided, such methods including the detection of levels of variety of biomarkers diagnostic of prostate cancer, including filamin A alone, or in combination with one or more additional biomarkers of prostate cancer, including, PSA, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3, filamin B, and LY9. Additionally, age can be used as a predictor variable. The invention also provides methods of treating prostate cancer which rely on diagnostic information obtained based on the detection of biomarkers of prostate cancer, including filamin A alone, or in combination with one or more additional biomarkers of prostate cancer, including, PSA, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, tubulin-beta 3, filamin B, LY9, and/or age. Compositions in the form of kits and panels of reagents for detecting the biomarkers of the invention are also provided.
Core Innovation
The invention relates to treating prostate cancer in a subject suspected of having prostate cancer by using diagnostic information derived from protein level measurements in a serum sample or a plasma sample. The subject is described as having elevated PSA and being symptomatic of prostate cancer, and the diagnostic information includes diagnostic information as to the protein level of filamin A.
The method determines whether the protein level of filamin A in the sample is increased relative to the protein level of filamin A in a normal control sample, and, based on that comparison, administers a therapeutically effective amount of an anti-cancer therapy. The anti-cancer therapy is selected from radiation therapy, chemotherapy, surgery for resecting tumor tissues, hormone therapy, antibody therapy, immunotherapy, cytokine therapy, growth factor therapy, or any combination of these.
In further embodiments, diagnostic information is obtained for one or more additional prostate cancer protein markers, and treatment is administered only if the protein level of filamin A and the protein level of at least one of the additional markers are increased relative to the corresponding levels in a normal control sample. The additional markers are selected from filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3.
Claims Coverage
The independent claims recite treating prostate cancer by comparing filamin A protein levels in serum or plasma from a subject with elevated PSA and symptoms against a normal control, and administering a therapeutically effective anti-cancer therapy from a defined treatment group when filamin A is increased relative to the normal control. Across the independent claims, the main inventive features include optional addition of one or more further prostate cancer protein markers and a concordant increase criterion for administering therapy. There are three independent claims in the provided set.
Filamin A-based treatment decision using serum or plasma and normal control comparison
Obtain a serum sample or a plasma sample from the subject, where the subject has elevated PSA and is symptomatic of prostate cancer, obtain diagnostic information as to the protein level of filamin A, and administer a therapeutically effective amount of an anti-cancer therapy if the protein level of filamin A in the sample is increased relative to the protein level of filamin A in a normal control sample.
Therapy selection from an anti-cancer therapy group when filamin A is increased
Administer a therapeutically effective amount of an anti-cancer therapy selected from radiation therapy, chemotherapy, surgery for resecting tumor tissues, hormone therapy, antibody therapy, immunotherapy, cytokine therapy, growth factor therapy, and any combination of these, when the filamin A protein level is increased relative to the normal control sample.
Multi-marker concordant elevation with additional prostate cancer protein markers
Obtain diagnostic information for the protein level of filamin A and at least one additional prostate cancer protein marker, and administer a therapeutically effective amount of the anti-cancer therapy if the protein level of filamin A and the protein level of at least one of the additional markers are increased relative to the protein level of filamin A and the protein level of at least one of the additional markers in a normal control sample.
Additional marker proteins selected from a defined panel
Select the one or more additional prostate cancer protein markers from filamin B, LY9, keratin 4, keratin 7, keratin 8, keratin 15, keratin 18, keratin 19, and tubulin-beta 3.
The independent claims are centered on using filamin A protein level measurements from serum or plasma with elevated PSA and prostate cancer symptoms, comparing the measured filamin A level to a normal control, and administering a therapeutically effective anti-cancer therapy from a defined set when filamin A is increased. Refinement aspects include concordant increases in filamin A plus at least one additional prostate cancer marker selected from a specified panel.
Stated Advantages
Enables diagnosis-based treatment selection for prostate cancer based on increased filamin A relative to a normal control sample.
Allows improved decision criteria by requiring increased filamin A and at least one additional prostate cancer marker relative to normal control levels.
Provides differentiated prostate cancer state assessment, including cancer versus normal and benign prostatic hyperplasia versus cancer, using filamin A in patient serum.
Documented Applications
Prostate cancer diagnosis, monitoring progression, prognosis, and therapy guidance using elevated serum/plasma filamin A protein levels.
Subject-state differentiation including cancer versus normal and benign prostatic hyperplasia versus cancer based on elevated filamin A.
Monitoring progression by changes in filamin A protein level over time, optionally with additional biomarkers.
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