SOCE Modulator Therapy for Metastatic Melanoma
Solution Overview
Problem
Current treatments for metastatic melanoma, such as targeted therapies and immunotherapies, face challenges with drug resistance and clinical toxicity, and there is a need for novel therapeutics that inhibit UV-supported progression of melanomagenesis.
Innovation Solution
Administering a composition that modulates store-operated Ca2+ entry (SOCE) using modulators like 4-((5-Phenyl-4-(trifluoromethyl)thiazol-2-yl)amino)benzoic acid (IA65) to elevate SOCE levels in cancerous cells, reducing their invasiveness, migration, and metastasis while maintaining normal SOCE levels in non-cancerous cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If targeted therapies (MAPK pathway inhibitors) are used to treat metastatic melanoma, then progression-free survival is transiently increased, but drug resistance and relapse occur followed by clinical toxicity due to immune cell function inhibition
Solution Approach 1:
The invention changes the therapeutic parameter from inhibiting MAPK pathway to modulating store-operated calcium entry (SOCE). By using calcium ionophores to increase intracellular calcium levels in melanoma cells, the treatment targets a different biological parameter that is essential for melanoma cell survival and metastasis, thereby avoiding resistance to MAPK inhibitors and reducing immune toxicity
Solution Approach 2:
The invention introduces calcium ionophores as intermediary substances that mediate the therapeutic effect. These compounds act as carriers to transport calcium ions into melanoma cells, elevating intracellular calcium levels and triggering apoptosis. This intermediary mechanism bypasses the need for direct MAPK pathway inhibition and avoids associated immune cell dysfunction
2Reliability
If immunotherapies (immune checkpoint inhibitors) are used to treat melanoma, then immune response is enhanced, but combined use with targeted therapies increases clinical toxicity
Solution Approach 1:
The invention shifts the therapeutic parameter from immune system modulation to direct calcium ion-mediated apoptosis in melanoma cells. By targeting intracellular calcium homeostasis in cancer cells specifically, the treatment achieves anticancer efficacy without the immune-mediated toxicity that occurs when combining immunotherapies with targeted therapies
3Object-affected harmful factors
If UV exposure is considered a risk factor for melanoma, then melanin production is induced to protect against UV damage, but UV also drives melanoma progression to vertical growth phase
Solution Approach 1:
The invention converts the harmful effect of UV-induced melanoma progression into a beneficial therapeutic opportunity. By targeting the calcium signaling pathway that is dysregulated in UV-exposed melanoma cells, the calcium ionophore treatment specifically addresses the progression mechanism while leaving normal melanin protective function intact
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 modulation of SOCE in cancer cells reduces their invasive and metastatic potential, providing a therapeutic approach that does not affect non-cancerous cells, thereby addressing the limitations of existing melanoma treatments.
Implementation Method 1
administering the to the subject a composition comprising at least one modulator of store-operated Ca2+ entry (SOCE)
Data Source
AI summary
The invention comprises methods for treating diseases or disorders associated with reduced levels of Ca2+ signaling, including melanoma and other cancers.