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Vacuolar ATPase and Drug Resistance of High Grade Gliomas

NCT05328089 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 20

Last updated 2024-01-03

No results posted yet for this study

Summary

GBMs are still considered tumors with few available treatment options that are able only to achieve a temporary local control of the disease. In case of a GBM, tumor recurrence is generally expected within 12 months and it is due to the presence of marginal tumoral cells with pro-oncogenic molecular phenotypes that are resistant to actual chemotherapies and to radiation therapy. Nowadays, surgery still represent the first treatment option in case of suspected GBM and it aims to remove the contrast enhancing lesion seen at the pre-operative brain MRI. In particular, the peripheral layer of the tumor is made of low replicating cellsglioblastoma-associated stromal cell (GASC) that can show different carcinogenic properties and that are probably responsible for tumor recurrence. Metabolism of GBMs is mainly anaerobialglicolisis that leads to the transformation of glucose in ATP and lactates. The production of high lactate levels determines a decrease of intracellular pH that is counterbalanced by V-ATPase activity through H+ ions extrusion from the intracellular to the extracellular environment. Increased V-ATPase activity affects different pro-tumoral activities and plays a crucial role in chemoresistance. In fact, a low extracellular pH can reduce the efficacy of antineoplastic agents since a low pH might affect the structural integrity of drugs and their ability to pass through the plasmatic membrane. Finally, V-ATPase can act as an active pump able to excrete antineoplastic agents. GBMs with high V-ATPAse expression are able to transmit malignant features and to activate proliferation of GASC in vitro through a network of microvescicles (MV) like exosomes and large oncosomes (LO) that transport cell to cell copy DNA (cDNA) and micro-RNAs (miRNA).In this view, our work is intended to study: 1) the effects of proton pump inhibitors (PPI) on CSC and GASCs cultures as in vitro add-on treatments; 2) the MVs load (in terms of miRNAs and cDNAs) during the neuro-oncological follow-up in order to understand how it changes after surgery and adjuvant treatments; 3) the possible roles of V-ATPase as a clinical marker to be used to check tumor response to adjuvant treatments.

Conditions

Sponsors & Collaborators

  • University of Milano Bicocca

    lead OTHER

Eligibility

Min Age
18 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-01-30
Primary Completion
2024-04-30
Completion
2024-04-30

Countries

  • Italy

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05328089 on ClinicalTrials.gov