Methods for diagnosing and treating metastatic cancer
Inventors
Lewis, John • Stoletov, Konstantin • Willetts, Lian
Assignees
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Publication Number
US-12421514-B2
Publication Date
2025-09-23
Expiration Date
Abstract
Disclosed are methods of diagnosing and treating metastatic cancer in a subject. The methods involve detecting or modulating the expression of at least one of Kif3b, ACTB, SRPK1, TM EM 229b, C14orf142, KB-1460A1.5, ACTC1, Nr2f1, KIAA0922, KDELR3, APBA2, miRNA 130b, miRNA 374b, or miRNA 122 in a biological sample from the subject.
Core Innovation
The invention relates to diagnostic and therapeutic approaches for metastatic cancer by detecting or modulating expression of multiple metastasis-associated genes and miRNAs. The targets described include Kif3b, ACTB, SRPK1, TMEM229b, C14orf142, Nr2f1, and miRNA-130b, miRNA-374b, and miRNA-122. The document positions these targets as associated with metastatic spread and invasive phenotypes.
The problem addressed is metastatic cancer spread, where the background motivation is that metastasis involves coordinated molecular changes and that interfering with metastasis-associated genes and miRNAs can prevent metastatic spread. The disclosure states that inhibiting the identified targets prevents metastatic spread. It further reports that the modulation of these targets affects metastatic burden, including measures of intravasation and extravasation.
For therapeutic effect, the document describes using gene silencing nucleic acid approaches directed to the metastasis-associated targets, including short interfering RNA, antisense oligonucleotide, short hairpin RNA, or ribozyme. It also provides supporting results linking miRNA-122 overexpression to blocked invasion and altered invasion along vasculature and collagen, with impaired MT1-MMP trafficking/localization and reduced extravasation. Bioinformatic and clinical database support is included indicating that the targets are upregulated in metastatic lesions and invasive zones across multiple human cancer types.
Claims Coverage
The provided material identifies one independent claim with multiple inventive features focused on preventing cancer metastasis by administering a gene-silencing nucleic acid inhibitor targeting specified metastasis-associated genes.
Gene-silencing nucleic acid inhibitor to prevent metastasis
Administering an effective amount of an inhibitor of at least one of Kif3b, SRPK1, TMEM229b, or Nr2f1 to prevent cancer metastasis in a subject, wherein the inhibitor is a gene silencing nucleic acid molecule comprising a short interfering RNA, an antisense oligonucleotide, a short hairpin RNA, or a ribozyme.
Targeted cancers associated with metastasis
Applying the method where the cancer metastasis is associated with melanoma, prostate, head and neck, lung, ovarian or colon cancer.
The independent claim covers a metastasis-preventing method using a gene-silencing nucleic acid inhibitor directed to at least one of Kif3b, SRPK1, TMEM229b, or Nr2f1, with the inhibitor limited to short interfering RNA, antisense oligonucleotides, short hairpin RNA, or ribozyme, for metastasis associated with specified cancer types.
Stated Advantages
Prevents metastatic spread.
Reduces metastatic burden, including intravasation/metastatic burden and reduced lung metastasis as described in the disclosure.
Blocks invasion associated with miRNA-122 overexpression.
Reduces extravasation associated with miRNA-122 overexpression.
Documented Applications
Preventing cancer metastasis in a subject for metastasis associated with melanoma, prostate, head and neck, lung, ovarian or colon cancer.
Diagnostic and therapeutic approaches for metastatic cancer by detecting or modulating expression of multiple metastasis-associated genes and miRNAs.
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