Mithramycin Analogue and Chemotherapeutic Agent Combination for TNBC
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Solution Overview
Problem
Current therapeutic options for triple-negative breast cancer (TNBC) are limited, with standard chemotherapy showing limited effectiveness due to rapid proliferation rates and DNA repair mechanisms, leading to frequent relapses and resistance, and there is a need for treatments with fewer adverse side effects.
Innovation Solution
A composition comprising a mithramycin analogue, specifically demycarosyl-3D-β-D-digitoxosyl-mithramycin SK, combined with chemotherapeutic agents such as taxanes, nucleoside analogs, or tyrosine kinase inhibitors, which are administered simultaneously, separately, or sequentially to enhance antitumoral effects while minimizing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard chemotherapy is used for TNBC treatment, then tumor growth inhibition is achieved, but treatment effectiveness is limited due to rapid proliferation rates and DNA repair mechanisms leading to resistance and relapses
Solution Approach 1:
The patent combines mithramycin analogue with conventional chemotherapeutic agents (taxanes, vinca alkaloids, platinum compounds) to create a synergistic treatment regimen. This combination addresses the limitation of single-agent chemotherapy by targeting multiple pathways simultaneously, overcoming the tumor's rapid proliferation and DNA repair mechanisms that cause resistance to monotherapy.
2Reliability
If mithramycin is used to sensitize TNBC cells to taxanes, then antitumoral effect is enhanced, but severe side effects limit its clinical use
Solution Approach 1:
The patent uses a mithramycin analogue with modified chemical structure (Formula I) that retains the ability to sensitize TNBC cells to taxanes while reducing severe side effects. The structural modification changes the toxicity profile while preserving the sensitizing mechanism, allowing clinical use at effective doses.
3Reliability
If combination therapy is used to overcome resistance, then treatment outcomes improve, but toxicity increases
Solution Approach 1:
The mithramycin analogue allows for optimized dosing regimens in combination therapy. By using the analogue instead of native mithramycin, the therapeutic window is improved, enabling combination regimens that achieve synergistic antitumoral effects while maintaining acceptable toxicity levels through reduced adverse side effects.
Data Source
AI summary
A composition comprising:a) a compound of Formula (I), or a salt, co-crystal or solvate thereof; andb) at least one chemotherapeutic agent, or a salt, co-crystal or solvate thereof, suitable for use in the treatment of breast cancer, preferably triple negative breast cancer.