Combination cancer therapies based on the mortalin targeting compound sheta2 and p53 reactivators or CDK4/6 inhibitors
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Solution Overview
Problem
Current maintenance therapies for ovarian cancer, such as PARP-1 inhibitors and angiogenesis inhibitors, fail to improve overall survival and are limited by significant side effects, with a high risk of secondary cancers and recurrence.
Innovation Solution
A synergistic drug combination of SHetA2, a mortalin-targeting compound, and PRIMA-1 MET<, a p53 reactivator, or CDK4/6 inhibitors like Palbociclib, Abemaciclib, or Ribociclib, to restore p53 activity and induce apoptosis in cancer cells, reducing tumor growth and recurrence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single agent is used at high dose to overcome resistance, then therapeutic effect may be improved, but toxicity increases
Solution Approach 1:
The treatment is divided into multiple components: a first cancer therapy agent and a second cancer therapy agent (or immunomodulator) are administered in combination, where each component contributes to overcoming resistance through different mechanisms rather than relying on a single high-dose agent
Solution Approach 2:
The dosing regimen is optimized by administering agents at specific dose ranges (e.g., first agent at 0.5-10 mg/kg, second agent at 1-20 mg/kg) and scheduling (e.g., every 2 weeks, every 3 weeks) to achieve therapeutic effectiveness while maintaining acceptable toxicity profiles
2Reliability
If combination therapy is used to overcome resistance and reduce toxicity, then therapeutic effect and safety are improved, but treatment complexity increases
Solution Approach 1:
The patent provides a universal combination therapy approach that can be applied across multiple cancer types and resistance scenarios. The first and second cancer therapy agents can be selected from broad categories of compounds with established mechanisms, allowing the regimen to address various resistance mechanisms (efflux pumps, metabolic pathways, apoptosis resistance) through a standardized combination strategy
Data Source
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AI summary
Drug combinations of a heteroarotinoid (e.g., SHetA2), and an Azabicyclooctan-3-one derivative (e.g., PRIMA-1 or PRIMAMET) and/or, a CDK4/6 inhibitor (e.g., Palbociclib, Abemaciclib, or Ribociclib), which are synergistically-effective as anti-cancer treatments, and kits and methods of use of such drug combinations.