ODC1-Guided DFMO Therapy for High-Risk Neuroblastoma Relapse
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Solution Overview
Problem
Current treatments for high-risk neuroblastoma, particularly in children, have poor long-term survival rates and are associated with severe side effects such as immunotherapy-induced pain, necessitating the development of new therapies that are both effective and less painful.
Innovation Solution
Administering α-difluoromethylornithine (DFMO) in combination with other agents like NSAIDs, polyamine transporter inhibitors, or immunomodulatory drugs, tailored by genetic testing for ODC1 allele genotypes, to target polyamine biosynthesis and prevent neuroblastoma recurrence or development.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-GD2 immunotherapy is administered to treat high-risk neuroblastoma, then event free survival and overall survival are increased, but intense visceral pain and allodynia occur as severe side effects
Solution Approach 1:
The patent introduces DFMO as an intermediary agent that modulates the immune response to anti-GD2 immunotherapy. DFMO acts as a polyamine biosynthesis inhibitor that reduces the severity of immunotherapy-associated pain while preserving the therapeutic anti-tumor effects, thereby mediating between the beneficial and harmful aspects of the treatment
2Productivity
If conventional chemotherapy and immunotherapy are used to treat high-risk neuroblastoma, then tumor response is achieved, but long-term survival remains poor at approximately 50%
Solution Approach 1:
The patent changes the biochemical parameters of tumor cells by inhibiting polyamine biosynthesis through DFMO administration. This parameter change affects tumor cell metabolism and growth, providing a new therapeutic mechanism that complements conventional chemotherapy and immunotherapy to improve long-term survival outcomes
3Stability of the object's composition
If intensive chemotherapy and immunotherapy protocols are administered, then initial tumor control is achieved, but >35% risk of relapse remains after completing upfront therapy
Solution Approach 1:
The patent applies DFMO therapy as a preliminary or maintenance treatment to prevent relapse. By administering DFMO before or after intensive chemotherapy and immunotherapy, the treatment addresses residual disease and prevents tumor recurrence, thereby reducing the >35% relapse risk associated with conventional protocols
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 approach improves survival rates and reduces side effects by selectively inhibiting polyamine biosynthesis, offering a targeted and well-tolerated treatment option for high-risk neuroblastoma patients.
Implementation Method 1
administering to the patient an effective amount of a pharmaceutical therapy comprising α-difluoromethylornithine (DFMO)
Data Source
AI summary
The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylornithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.