CARP-1 Binding Compounds to Overcome Doxorubicin Resistance
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Solution Overview
Problem
Cancer cells develop resistance to chemotherapeutic agents like doxorubicin, hindering effective treatment, and diverse pathways of cell survival and apoptosis signaling by the transcription factor NF-κB remain elucidated.
Innovation Solution
Compounds and compositions targeting CARP-1, a perinuclear phospho-protein, are developed to inhibit its signaling and enhance the efficacy of chemotherapeutic agents in treating various cancers by inhibiting cell cycle progression, cell growth, and DNA repair.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If doxorubicin is used to treat cancer, then cancer cell death is induced, but cancer cells develop resistance reducing treatment efficacy
Solution Approach 1:
The patent introduces CARP-1 as an intermediary protein that mediates between doxorubicin and NF-κB signaling. By targeting CARP-1 with specific compounds, the treatment indirectly modulates NF-κB activity and overcomes resistance mechanisms. The CARP-1 binding compounds serve as intermediaries that restore sensitivity to doxorubicin without directly being the primary cytotoxic agent.
Solution Approach 2:
The patent identifies and utilizes the structural and functional characteristics of CARP-1 to design compounds that replicate its ability to modulate NF-κB signaling. The compounds copy the essential binding properties of natural CARP-1 peptides while achieving enhanced stability and potency, effectively recreating the resistance-overcoming mechanism in a drugable format.
2Reliability
If NF-κB signaling is inhibited to overcome resistance, then cancer cell survival is reduced, but normal cell survival pathways may be affected
Solution Approach 1:
The patent employs local quality by designing compounds that specifically target the CARP-1-NF-κB interaction interface with high precision. The molecular structures are optimized to bind only to specific epitopes on CARP-1 or NF-κB, ensuring that NF-κB inhibition occurs locally at the cancer cell pathology site rather than systemically affecting all NF-κB dependent processes in normal tissues.
Solution Approach 2:
The patent utilizes parameter changes by modifying physical and chemical properties of the inhibitor compounds to achieve selective cancer cell targeting. Parameters such as molecular weight, hydrophobicity, charge distribution, and binding affinity are carefully tuned to ensure the compounds penetrate cancer cells effectively while being excluded from or having minimal impact on normal cells with intact regulatory mechanisms.
3Reliability
If CARP-1 binding compounds are developed to overcome resistance, then treatment outcomes improve, but drug development complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the complex drug development process into distinct modules: (1) identification of CARP-1 as the target, (2) characterization of the CARP-1-NF-κB interaction, (3) design of peptide-based inhibitors, (4) optimization of compound properties, and (5) preclinical validation. This segmented approach allows each stage to be independently optimized and validated, reducing overall development complexity despite the sophistication of the solution.
Data Source
AI summary
The present disclosure is concerned with compounds and compositions for use in the prevention and treatment of cancer such as, for example, a primary or secondary tumor within a subject's brain, breast, kidney, pancreas, lung, colon, prostate, lymphatic system, liver, ovary, or cervix. Additional examples of cancers for which the disclosed compounds and compositions can be useful include, but are not limited to, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanomas, gliomas, leukemia, lymphoma, chronic myeloproliferative disorders, myelodysplastic syndrome, myeloproliferative neoplasm, non-small cell lung carcinomas, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.