Ignite Creation Date:
2024-05-06 @ 8:21 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06348693
Status:
RECRUITING
Last Update Posted:
2024-04-05
First Post:
2024-03-21
Brief Title:
Development of Therapeutic Approaches Modulating Molecular Targets Implicated on Cancer Stem Cell-related Aggressiveness
Sponsor:
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Organization:
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Study Overview
Official Title:
Strategies for the Development of Multimodal Therapies in Tumors of the Central Nervous System Identification of New Molecular and Metabolic Targets Implicated in Survival and Chemoresistance Involving Endothelial and Cancer Stem Cells
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Tumors of the central nervous system affect 21 people per 100000 every year a figure that refers to countries with advanced economies with an increase in incidence over time Experimental evidence suggests that cancer stem cells CSCs may play a key role in the malignancy of these tumors In fact due to the hypoxic tumor microenvironment these cells are able to create compensatory pathways that confer stem-like angiogenic and pro-tumoral functions Furthermore it has been demonstrated that brain tumor stem cells are radio- and chemo-resistant and therefore not treatable with the therapeutic protocols currently in use To date in fact there are no definitive treatments for the eradication of brain tumors In this scenario sphingolips a class of lipid deputized to several physiological functions are also involved in tumor onset progression drug resistance and aggressiveness In hypoxic tumor microenvironment CSCs present a modified rheostat in the metabolism of sphingolipid in favor of Sphingosine-1-phosphate S1P
S1P is an intermediate of sphingolipid metabolism formed from sphingosine through the action of sphingosine kinases SK Increasing evidence suggests that S1P acts as a tumor-promoting signal predominantly in the extracellular environment regulating important cellular properties correlated with tumor potential
The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment
S1P is an intermediate of sphingolipid metabolism formed from sphingosine through the action of sphingosine kinases SK Increasing evidence suggests that S1P acts as a tumor-promoting signal predominantly in the extracellular environment regulating important cellular properties correlated with tumor potential
The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment
Detailed Description:
Tumors of the central nervous system affect 21 people per 100000 every year a figure that refers to countries with advanced economies with an increase in incidence over time Among tumors of the central nervous system Glioblastoma GBM is the most frequent and aggressive malignant tumor with an average life expectancy of approximately 12 months and a survival of less than 5 in the following 5 years to the diagnosis The growth and progression of GBM are dependent on a specialized subpopulation of tumor cells called cancer stem cells CSCs CSCs are chemo- and radio-resistant are responsible for relapses and therefore should constitute an important target of therapeutic strategies but the mechanisms underlying their biology are still poorly understood Hypoxia through the hypoxia-inducible factor HIF and sphingolipid pathway plays a key role in the control of tumor growth and angiogenesis and represents perhaps the most effective adaptation mechanism of the tumor itself Indeed The hypoxic microenvironment of solid tumors gives them greater aggressiveness an increase in the expression of proteins linked to angiogenesis anaerobic energy metabolism and adaptation to oxidative stress which facilitates the onset and proliferation of CSCs
This study supports the evidence that the hypoxic microenvironment regulates the state of CSCs and therefore influencing the response to the current pharmacological treatments
Although S1P can act as an intracellular second messenger most of its effects are exerted as an extracellular mediator through binding to specific G protein-coupled receptors originally known as EDGs and now called S1P receptors S1PRs Our group has previously demonstrated that acquired modifications in the metabolism of sphingolipids in particular in the regulation of S1P are able to confer stem-like and chemo-resistance properties to CSCs in patients with GBM
The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment
Through the study of sphingolipid metabolism new markers and inhibitors will be identified to be delivered to inhibit CSC proliferation and tumor progression
With this approach the investigators will be able to evaluate how the tumor microenvironment and the molecular and metabolic characteristics of the tumor influence cellular communication and whether this process can be influenced by new pharmacological treatments This study could highlight new pathways and tumor-specific alterations to stratify new therapeutic strategies and to identify new potential biomarkers in diagnosis and monitoring thus improving the prognosis of patients suffering from brain tumors
This study supports the evidence that the hypoxic microenvironment regulates the state of CSCs and therefore influencing the response to the current pharmacological treatments
Although S1P can act as an intracellular second messenger most of its effects are exerted as an extracellular mediator through binding to specific G protein-coupled receptors originally known as EDGs and now called S1P receptors S1PRs Our group has previously demonstrated that acquired modifications in the metabolism of sphingolipids in particular in the regulation of S1P are able to confer stem-like and chemo-resistance properties to CSCs in patients with GBM
The project aims to identify new molecular and metabolic targets involved in the survival and chemo-resistance of tumor stem cells in relation to the tumor microenvironment
Through the study of sphingolipid metabolism new markers and inhibitors will be identified to be delivered to inhibit CSC proliferation and tumor progression
With this approach the investigators will be able to evaluate how the tumor microenvironment and the molecular and metabolic characteristics of the tumor influence cellular communication and whether this process can be influenced by new pharmacological treatments This study could highlight new pathways and tumor-specific alterations to stratify new therapeutic strategies and to identify new potential biomarkers in diagnosis and monitoring thus improving the prognosis of patients suffering from brain tumors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None