Personalized medicine is the new frontier in the treatment of cancer. This study aims at setting up a predictive in vitro model of the clinical response of cancer patients to recently introduced treatments (target therapy, electrochemotherapy) and to new potential therapies. The necessity of personalized therapy tailored on the necessities of the patients is of paramount importance; to obtain such a degree of personalization is fundamental to use an experimental model that resemble the characteristics of the tumor in vivo such as tridimensionality and cell-cell and cell matrix interactions. One of the most common and lethal tumor type is metastatic melanoma. This work aims at setting up a platform for the screening of novel drugs against metastatic melanoma (targeted therapy) in combination with electrochemotherapy in melanoma spheroids. During the first phase of the study cells from a human melanoma cell line (A375) will be used to generate spheroids, a 3D culture model, or will be seeded in hyaluronic acid scaffolds and/or self-aggregating pep tide matrices, to resemble the microenvironment of the tumor and to allow the tumor cells to generate their own extracellular matrix. Once the in vitro 3D model of tumor tissue is characterized, these scaffolds will be used to test different drugs and their dosages in matrices seeded with cells derived from melanoma patients. Patients with in-transit melanoma metastases will be the source of cancer cells. After informed consent, cells from human in transit nodules will be separated, sorted, and cultured. Electrochemotherapy will be then applied to 3D cell cultures to increase the uptake of drug molecules by the cancer cells, decreasing the drug dosage. The effects of the treatment will be assessed by evaluating the spheroid growth and morphology, extracellular matrix production, gene ex pression, expression of membrane receptors (e.g. MC1R) and secondary messengers (cAMP)
Electrochemoterapy in personalized medicine. A predictive in vitro model for electrochemotherapy in metastatic melanoma
Nicolò Martinelli;Annj Zamuner;Monica Dettin;Luigi Dall’Olmo;Luca Menilli;Maria Teresa Conconi
2024
Abstract
Personalized medicine is the new frontier in the treatment of cancer. This study aims at setting up a predictive in vitro model of the clinical response of cancer patients to recently introduced treatments (target therapy, electrochemotherapy) and to new potential therapies. The necessity of personalized therapy tailored on the necessities of the patients is of paramount importance; to obtain such a degree of personalization is fundamental to use an experimental model that resemble the characteristics of the tumor in vivo such as tridimensionality and cell-cell and cell matrix interactions. One of the most common and lethal tumor type is metastatic melanoma. This work aims at setting up a platform for the screening of novel drugs against metastatic melanoma (targeted therapy) in combination with electrochemotherapy in melanoma spheroids. During the first phase of the study cells from a human melanoma cell line (A375) will be used to generate spheroids, a 3D culture model, or will be seeded in hyaluronic acid scaffolds and/or self-aggregating pep tide matrices, to resemble the microenvironment of the tumor and to allow the tumor cells to generate their own extracellular matrix. Once the in vitro 3D model of tumor tissue is characterized, these scaffolds will be used to test different drugs and their dosages in matrices seeded with cells derived from melanoma patients. Patients with in-transit melanoma metastases will be the source of cancer cells. After informed consent, cells from human in transit nodules will be separated, sorted, and cultured. Electrochemotherapy will be then applied to 3D cell cultures to increase the uptake of drug molecules by the cancer cells, decreasing the drug dosage. The effects of the treatment will be assessed by evaluating the spheroid growth and morphology, extracellular matrix production, gene ex pression, expression of membrane receptors (e.g. MC1R) and secondary messengers (cAMP)
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