Engineered Peptide Inhibits p110beta to Overcome Chemoresistance
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Solution Overview
Problem
Current treatments for cancers like glioblastoma and melanoma face challenges due to resistance to chemotherapy, particularly attributed to aberrant PI3K expression and activity, where existing therapies are ineffective against chemoresistant cancers with overexpression of p110beta.
Innovation Solution
Engineered peptides comprising a p110beta targeting peptide coupled with a cell penetrating delivery moiety, which selectively inhibit p110beta activity, are used in conjunction with connexin 43 inhibitors and chemotherapeutics like temozolomide to enhance treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapeutics are used to treat cancer, then treatment is provided for sensitive cancers, but treatment effectiveness is lost in cancers with chemoresistance involving p110beta overexpression
Solution Approach 1:
The patent uses a peptide inhibitor as an intermediary substance that specifically binds to and inhibits p110beta, the molecular mediator responsible for chemoresistance. This peptide acts as a bridge between the chemotherapeutic agent and the resistant cancer cells, restoring sensitivity by blocking the aberrant PI3K signaling pathway that confers resistance.
Solution Approach 2:
The invention changes the biochemical parameter of p110beta activity by introducing a peptide inhibitor that specifically targets and suppresses this enzyme's function. By altering the activity level of p110beta from overactive (resistant state) to inhibited (sensitive state), the treatment becomes effective against previously resistant cancers.
2Measurement precision
If peptide inhibitors are designed to selectively target p110beta, then specificity against p110beta is improved, but delivery into cells becomes challenging
Solution Approach 1:
The patent merges two distinct functional components into a single peptide molecule: the p110beta-targeting sequence that provides selective binding affinity, and the cell-penetrating peptide sequence that enables efficient cellular internalization. This combined structure simultaneously achieves both high selectivity and effective delivery without requiring separate administration of multiple agents.
Solution Approach 2:
The engineered peptide performs multiple functions within a single molecular entity: it acts as both a targeting ligand for p110beta and a delivery vehicle for cellular entry. This multi-functionality eliminates the need for separate targeting and delivery mechanisms, simplifying the therapeutic approach while maintaining both selectivity and 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 engineered peptide combination effectively targets and inhibits p110beta activity, overcoming chemoresistance in cancers with p110beta overexpression, thereby improving treatment outcomes for resistant cases of glioblastoma and melanoma.
Implementation Method 1
the delivery moiety is a cell penetrating peptide
Implementation Method 2
the p110beta targeting peptide is capable of selectively binding p110beta or a complex thereof, selectively inhibiting p110beta activity
Data Source
AI summary
Described herein are compositions and formulations to treat and/or prevent a PI3K mediated disease or a symptom thereof in a subject in need thereof. In some embodiments, such compositions include engineered peptides capable of targeting PI3K or Connexin 43. Also described herein are methods of treating and/or preventing PI3K mediated disease or a symptom thereof. In some embodiments, the PI3K mediated disease is a cancer.