Project type: Fundamental and Groundbreaking Research, Exploratory Research Projects, within The National Plan for Research, Development and Innovation, PNIII
Project code: PN-III-P4-PCE-2021-1572
Project type: Fundamental and Groundbreaking Research, Exploratory Research Projects, within The National Plan for Research, Development and Innovation, PNIII
Project code: PN-III-P4-PCE-2021-1572
Project type: Fundamental and Groundbreaking Research, Exploratory Research Projects, within The National Plan for Research, Development and Innovation, PNIII
Programme 4
Title: Metallomics modulation of membrane transporters in chemoresistant ovarian cancer cells through nano-sensitizers
Romanian: Modularea metalomica a transportorilor membranari in celulele tumorale ovariene chimiorezistente cu ajutorul nano-sensibilizatorilor
Project code: PN-III-P4-PCE-2021-1572
Granted by: UEFISCDI -Executive Agency for Higher Education, Research, Development and Innovation Funding in Romania
Contract no: PCE105/2022
Total funding: 1.200.000 RON (~ 250.000 Euro)
Period: June 2022-December 2024 (37 months)
Host Institution: Institute of Oncology “Prof.Dr. Ion Chiricuta” , 34-36 Republicii, 400015 Cluj-Napoca, Romania, website: www.iocn.ro
Project director: EVA FISCHER-FODOR, Ph.D., Senior Researcher I
Brainmap: U-1700-038Y-1894; ORCID: 0000-0002-0898-0547; ResearcherID: C-4506-2011
The MetallomeX project is a fundamental biomedical research project, which proposes to apply a scientific domain in progress: metallomics,
aiming to reprogram the chemoresistance of ovarian cancer cells using novel metal-based nanostructures capable to re-sensitize the
tumor cell.
By integrative characterization of membrane transporters involved in chemoresistance, by metallomic mapping of
ovarian tumor cells and by highlighting the cell death pathways induced by metal drugs such apoptosis and
ferroptosis, potential druggable targets will be identified.
Our aim is to reveal predictive or prognostic biomarkers, to validate these biomarkers, to find new targeted
compounds, prone to be translated towards clinical studies. The project envisage a disease that severely affects
the quality of life and reduces the life expectancy of many women diagnosed from Romania and from the World, and
the activities of the project are in concordance with the principles of the National Anti-Cancer Programme
.
The host in the Oncology Institute “Prof.Dr. Ion Chiricuta” Cluj-Napoca , member of the Organization
of European Institutes of Oncology (OECI) and the project is implemented by a multi- and interdisciplinary team
with international visibility, in order to obtain an adequate dissemination of results and judicious use of
resources provided by the grant authority.
Project director:
Sr. Res. I. Eva FISCHER-FODOR
Scientific Coordinator:
Prof. Patriciu ACHIMAS-CADARIU, MD, PhD.
Participants:
Assoc.Prof.Catalin Ioan VLAD, MD, Ph.D.
Prof. Eugen Stelian GURZAU, MD., Ph.D.
Sr. Res.I. Piroska VIRAG, Ph.D.
Sr. Res.I. Ovidiu BALACESCU, Ph.D.
Prof. Mihai Cosmin CENARIU, Ph.D.
Sr.Res. I. Monica Olivia FOCSAN, PhD.
Paul Milan KUBELAC, MD, PhD
Bogdan POP, MD, PhD
Anca Meda BURCA, PhD
Raluca LAPUSAN, Ph.D., postdoctoral researcher
Andrei PASCA, M.D., Ph.D. Student
Anamaria GREC, PhD. Stud.
The MetallomeX project proposes to decrease the chemoresistance in ovarian cancer cells through metal-functionalized
nano-embedded compounds, sensitizers able to modulate the tumour cell signalling, with emphasize on pathways linked to the
metals membrane trafficking The main objectives and the proposed activities of the work plan are the followings:
• Metallomic mapping of chemoresistant ovarian cancer cells will be achieved through the following activities
• Assessment of the cellular uptake/extrusion balance of standard platinum drugs, and novel metal-based compounds in relation to the membrane transport
• Resensitization of chemoresistant cells by core-shell type targeted nanostructures loaded with platinum and novel synthesized metal complexes
• Clinical validation of the in vitro 3-D cell culture results
The projects aim is to elucidate important aspects of the ovarian chemoresistance, especially the resistance
towards platinum drugs, in this case carboplatin being envisaged.
The aim is to establish a relationship between the ovarian tumor cells metal homeostasis and the acquired
chemoresistance, through the balance between platinum and essential and non-essential minerals uptake and
trafficking through the cell.
They will be studied the solute carrier transporters and the ATP-binding cassette multidrug transporters with
relevance in the ovarian cancer and preclinical tests will be performed on FDA-approved drugs that target the
mineral imbalance, and novel functionalized materials. We expect to identify drugs that could positively
influence in vitro the platinum or other metals uptake into ovarian tumor cells, by their administration as
adjuvant along the standard medication and to propose their repurposing to counteract the drug resistance.
Novel compounds and nanostructures will be developed to target the metal trafficking and other features of
chemoresistance in ovarian tumors.
The results will be disseminated by means of scientific papers in journals indexed by Web of Science - Core Collection InCites Journal Citation Reports, oral presentations, proceedings, measurement reports, guides, and method whitepapers.
Scientific Report Phase I 2022
Our accomplished activities in the first two phases of the project, between June 2022 and December 2023 are the followings:
A1.1. Integrative characterization of the SLC membrane transporters and ABC extrusion pumps in platinum-resistant ovarian cancer cells
A1.2. Membrane marker identification at single cell level
A1.3. Evaluation of the soluble secreted SLC and ABC proteins
A1.4. Assessment of the intracellular metal elements in platinum-sensitive vs. platinum-resistant cells
A2.1 Establishment of cellular death mechanisms triggered by platinum-based drugs, platinum-functionalized nanostructures and novel metal complexes
A2.2. Assessment of ferroptosis, the "metallomic cell death" through the platinum-iron balance in relation to the membrane transporters and oxidative stress signals
A2.3. Evaluation of the nanoparticles modulatory effect on the oxidative stress-mediated ferroptotic signaling in chemoresistant ovarian cancer cells.
We invite you to read our new paper :
Cytotoxicity evaluation of unmodified paddlewheel dirhodium(II,II)-acetate/-formamidinate complexes and their axially modified low-valent metallodendrimers,
https://doi.org/10.3390/molecules28062671 .
Rezumat executiv al activităților realizate în etapa a II‐a de implementare
Tumor Biology Department
Institutute of Oncology “Prof.Dr. Ion Chiricuta”, 34-36 Republicii, 400015 Cluj-Napoca, România
Tel: +40-264-598 361/int 145
Fax: +40-264-439260
E-mail: fischer.eva@iocn.ro