Hsp90 Inhibitor and Platinum Agent Combination Therapy
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Solution Overview
Problem
Current chemotherapy for cancer is often unsatisfactory due to its limited effectiveness against complex genetic abnormalities in signaling pathways, and existing treatments tend to have significant side effects, making them less effective for patients with certain types of cancer.
Innovation Solution
The use of specific triazolone Hsp90 inhibitors in combination with platinum-containing anti-cancer agents, such as cisplatin, to treat proliferative disorders like cancer, particularly those with mutations or translocations in EGFR, K-Ras, c-Met, c-Kit, HER2, B-Raf, PI3K, and ALK proteins, to enhance treatment efficacy while minimizing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemotherapy agents are used to treat cancer, then some anticancer effect is achieved, but the treatment effectiveness is limited due to complex genetic abnormalities in signaling pathways
Solution Approach 1:
The patent combines Hsp90 inhibitors with platinum-containing chemotherapy agents to create a combination therapy that addresses multiple genetic abnormalities simultaneously. The Hsp90 inhibitor targets heat shock proteins involved in protein folding and stability, while the platinum agent targets DNA, creating a multi-targeted approach that overcomes the limitation of single-agent chemotherapy against complex genetic abnormalities in signaling pathways
2Reliability
If higher doses of chemotherapy agents are used to improve treatment effectiveness, then anticancer effects are enhanced, but side effects increase significantly
Solution Approach 1:
By combining Hsp90 inhibitors with platinum-containing agents at optimized doses, the patent achieves enhanced anticancer effects through synergistic action while maintaining side effect profiles within acceptable ranges. The combination allows each agent to work at lower effective doses compared to monotherapy, reducing individual toxicity while achieving greater overall therapeutic benefit
3Ease of operation
If single-target chemotherapy agents are used, then treatment is simpler, but effectiveness is reduced against cancers with multiple genetic abnormalities
Solution Approach 1:
The patent merges Hsp90 inhibition with platinum-based chemotherapy to create a two-agent regimen that addresses multiple genetic abnormalities in signaling pathways. This combination provides broader coverage against diverse cancer types and genetic variations while maintaining a relatively simple administration protocol, balancing treatment complexity with therapeutic effectiveness
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
This combination therapy demonstrates significant anticancer effects, including reduced development of drug-resistant cancer cells, allowing for a potentially lower dose of platinum-containing agents and improved treatment outcomes in various cancer types.
Implementation Method 1
Inhibition of Hsp90 results in the degradation of its client proteins via the ubiquitin proteasome pathway
Implementation Method 2
platinum-containing anti-cancer agent combinations are surprisingly effective at treating subjects with certain cancers
Data Source
AI summary
A pharmaceutical combination comprising a platinum-containing anticancer agent, and an Hsp90 inhibitor according to the following formulae (I) & (Ia), a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables structural formulae are defined herein. Also provided is a method of treating a proliferative disorder such as cancer in a subject in need thereof, using the pharmaceutical combination described herein.