AAC-11 Peptides Membrane Disruption for Resistant Cancer
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Solution Overview
Problem
Current cancer treatments are limited as they do not effectively induce cell death in cancer cells with disrupted pathways or treatment-resistant cancers, necessitating the development of new therapeutic approaches that can target various types of cancer.
Innovation Solution
AAC-11-derived peptides specifically target the plasma membrane of cancer cells, inducing rapid cell death through membranolysis and inhibiting cell migration and invasion, with in vivo studies demonstrating their effectiveness in inhibiting tumor growth in mouse models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional cancer treatments are used, then they can treat some types of cancer, but they are ineffective against cancer cells with disrupted pathways or treatment-resistant cancers
Solution Approach 1:
The invention changes the mechanism of action from conventional apoptosis-inducing pathways to a physical membrane disruption mechanism. The peptide adopts an alpha-helical conformation that inserts into and disrupts the plasma membrane, causing cell death through membranolysis rather than through protein synthesis or pathway-dependent apoptosis, thereby overcoming treatment resistance
Solution Approach 2:
The peptide is designed to mimic the membrane-disrupting properties of natural antimicrobial peptides. By copying the structural features (amphipathic alpha-helical conformation) and mechanism of action of these natural peptides, the invention creates a therapeutic agent that can effectively target and disrupt cancer cell membranes regardless of their specific molecular pathways
2Adaptability or versatility
If new therapeutic approaches are developed to target various cancer types, then treatment versatility improves, but the complexity of identifying effective targets increases
Solution Approach 1:
The peptide is designed with universal membrane-disrupting properties that make it effective across multiple cancer types. The amphipathic alpha-helical structure allows it to interact with and disrupt plasma membranes of diverse cancer cells through a common mechanism, eliminating the need for cancer-type-specific targeting strategies
Solution Approach 2:
The invention extracts and utilizes only the essential membrane-disrupting functional domain (residues 377-399) from the larger AAC-11 protein. This extracted peptide fragment retains the critical ability to adopt an alpha-helical conformation and disrupt membranes, simplifying the therapeutic agent while maintaining broad efficacy
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The AAC-11 peptides selectively disrupt vital cellular functions in cancer cells, inducing tumor cell death and inhibiting tumor growth across various cancer types, including non-small cell lung cancer and triple-negative breast cancer, with potential for wide therapeutic activity regardless of tumour suppressor p53 status.
Implementation Method 1
the peptides specifically target the plasma membrane of cancer cells... induce a rapid cell death through membranolysis of cancer cells
Data Source
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Figure 1C~2A
AI summary
The present invention relates to methods and pharmaceutical compositions for the treatment of cancer. In particular, the present invention relates to a polypeptide comprising or consisting of i) an amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1 or, ii) an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1, or iii) an amino acid sequence which is a retro-inverso of the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1 or, iv) an amino acid sequence which is retro-inverso of the amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the phenylalanine residue at position 380 to the leucine residue at position 384 in SEQ ID NO: 1.