DOC1 Polypeptide Fragments Inhibit Angiogenesis
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Solution Overview
Problem
Current anticancer therapies are inadequate in effectively inhibiting tumor angiogenesis, a crucial process for tumor growth and spread, as existing methods lack specific and efficient targets for angiogenic regulation.
Innovation Solution
The use of DOC1 (FILIP1L) polypeptides and their fragments, which exhibit anti-angiogenic, anti-proliferative, and apoptotic activities, are employed to inhibit cell proliferation, migration, and tumor growth by targeting endothelial cells and tumor vasculature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anticancer therapies are used, then cancer treatment is provided, but tumor angiogenesis is not effectively inhibited
Solution Approach 1:
The patent identifies and modulates specific gene expression parameters (DOC1, KLF4, TC-1) that regulate angiogenesis. By changing the expression levels of these genes through therapeutic intervention, the patent achieves effective inhibition of tumor angiogenesis, resolving the contradiction between providing cancer treatment and effectively blocking tumor blood vessel formation.
Solution Approach 2:
The patent uses DOC1 as an intermediary target that mediates between angiogenesis inhibitors and downstream effectors (KLF4, TC-1). By targeting DOC1 expression and function, the patent creates a controlled mechanism that effectively inhibits angiogenesis while managing the complexity of tumor biology.
2Reliability
If angiogenesis inhibitors are used to modulate gene expression, then tumor angiogenesis is inhibited, but the mechanism of action is not fully understood
Solution Approach 1:
The patent establishes feedback loops by identifying DOC1 as an upstream regulator of KLF4 and TC-1. This feedback mechanism allows the patent to understand how angiogenesis inhibitors work at the molecular level, resolving the contradiction between achieving angiogenesis inhibition and understanding the underlying mechanism.
Solution Approach 2:
The patent segments the angiogenesis regulation pathway into distinct functional components: DOC1 as the primary regulator, KLF4 and TC-1 as downstream effectors. This segmentation enables the patent to systematically study and explain the mechanism of action, transforming the black box of angiogenesis inhibition into a understood multi-step process.
3Reliability
If DOC1 expression is targeted for therapy, then anti-angiogenic activity is achieved, but DOC1 function was previously unknown
Solution Approach 1:
The patent uses cDNA microarray analysis to create a functional copy of the DOC1 gene expression pattern across different cell types and disease states. By analyzing the copied expression data, the patent inferred DOC1's anti-angiogenic function despite the protein's previously unknown role, resolving the contradiction between achieving therapy and understanding the target's function.
Data Source
AI summary
A purified DOC1 polypeptide comprising a fragment of SEQ ID NO:1 is provided, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence. A method of inhibiting angiogenesis in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting angiogenesis. A method of inhibiting tumor growth in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting tumor growth.