FRRB Project 1731093 - Interrogating circulating lung tumor cells to guide personalized therapies and identify novel targets to hit metastasis initiating cells
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Name and Surname of PI |
Giulia Bertolini |
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Project Acronym |
CTC Mining |
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Project ID |
1731093 |
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Host Institution |
Fondazione IRCCS Istituto Nazionale per lo studio e la cura dei Tumori - Milan |
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Pathology of Interest |
Lung Cancer |
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Research Area |
Oncology |
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Project Start Date |
1 April 2021 |
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Project End Date |
31 March 2024 |
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Funding |
€ 574.660,00 |
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Type of Project |
Individual |
PROJECT SUMMARY
The CTC-Mining project aims at studying, in patients with lung cancer undergoing neo-adjuvant chemotherapy, the features of circulating tumor cells (CTC) responsible for metastasis initiation, in order to select patients who can benefit the most from chemotherapy and to find novel and more effective combination therapies.
Patients enrolled in the study are monitored through blood sampling which allows CTC analysis before/after chemotherapy and after surgery/disease recurrence.
Our data indicate that detection of a low number of CTCs expressing CXCR4 protein, before therapy, is associated with a better response to chemotherapy and better long-term survival. Furthermore, the modulation of CTC with metastatic phenotype (CD133/CXCR4) after chemotherapy or after surgery could provide important information on the patient's prognosis. These results could, therefore, allow a more rational selection of patients with lung cancer eligible for chemotherapy, reducing NHS costs and toxic treatments for some patients; moreover, it could allow a rapid CTC-based monitoring of therapy efficacy and timely clinical intervention.
We have optimized innovative strategies for the molecular study of CTCs at single cell level, in order to identify new targets to develop specific therapies against the cells responsible for metastases. We have identified a protein (CDH11) essential for the maintenance of cancer cells with high metastatic potential, that could represent a very promising therapeutic target to increase the anti-metastatic effectiveness of chemotherapy.
We have also developed and tested a promising molecular test that allows the rapid identification of metastatic CTCs in blood, that will be improved and refined in the next year of the project. This easy and cost-effective test could be applied in clinical practice to rapidly evaluate therapy response and prognosis of patients by providing a window of opportunity to tailor effective therapy for each patient.