TESTA CAROLINA | Cycle: XXXVI |
Section: Computer Science and Engineering
Advisor: CERI STEFANO
Tutor: CAPPIELLO CINZIA
Major Research topic:
Drug repurposing for migrastatic agents
Abstract:
My doctoral project is focused on drug repurposing in the field of migrastatic agents. A migrastatic drug is a drug that should ideally interfere with the ability and possibility of cancer cells to migrate, thus preventing them from escaping from the primary tumor and from metastasizing elsewhere in the body. To date, the commonly used drugs and those on which the greatest research effort is employed are called cytostatics, since they are more directed against cell proliferation and are evaluated for their ability to cause tumor shrinkage. However, in solid tumors, 90% of mortality is caused by the invasion of cancer cells that have acquired resistance to cytostatic drugs and have consequently formed metastases. For this reason, it seems very important to start focusing on migrastatic, or anti-metastatic, drugs as they could define new options for the therapy of solid tumors.
The normal process of developing a new drug is extremely expensive and time-consuming. In addition, in most cases, compounds that succeed in vitro and animal tests are then blocked at stage I of clinical trials, because of their inefficiency or excessive toxic effects. In recent years, the use of biological and medical big data has been considered in order to investigate new therapeutic possibilities for drugs that have already been approved and are therefore already on the market and commonly used, as well as to study their actions and side effects. To do this, we use a network-based approach that allows to integrate data of different types (drugs, genes, pathways, etc.).The basic idea of the project is therefore to perform a drug repurposing operation to identify already approved drugs which are used for other purposes, and which may be possible candidates such as migrastatics, or anti-metastatic, drugs thus using an ad hoc network focused on migration aspects and the process of metastases formation. Once possible candidates are identified, we test them in vitro, using a particular scaffold called NICHOID. The NICHOID is obtained by means of a two-photon polymerization technique, which has a very high resolution (in the order of µm) that allows the creation of a geometry controllable at the cellular level. The fundamental aspect is the three-dimensionality that the scaffold provides to the cells, allowing them to grow in a much more realistic environment, more similar to the in vivo one when compared with normal culture plates, thus providing a much more reliable response to external stimuli (e.g. drugs).
The normal process of developing a new drug is extremely expensive and time-consuming. In addition, in most cases, compounds that succeed in vitro and animal tests are then blocked at stage I of clinical trials, because of their inefficiency or excessive toxic effects. In recent years, the use of biological and medical big data has been considered in order to investigate new therapeutic possibilities for drugs that have already been approved and are therefore already on the market and commonly used, as well as to study their actions and side effects. To do this, we use a network-based approach that allows to integrate data of different types (drugs, genes, pathways, etc.).The basic idea of the project is therefore to perform a drug repurposing operation to identify already approved drugs which are used for other purposes, and which may be possible candidates such as migrastatics, or anti-metastatic, drugs thus using an ad hoc network focused on migration aspects and the process of metastases formation. Once possible candidates are identified, we test them in vitro, using a particular scaffold called NICHOID. The NICHOID is obtained by means of a two-photon polymerization technique, which has a very high resolution (in the order of µm) that allows the creation of a geometry controllable at the cellular level. The fundamental aspect is the three-dimensionality that the scaffold provides to the cells, allowing them to grow in a much more realistic environment, more similar to the in vivo one when compared with normal culture plates, thus providing a much more reliable response to external stimuli (e.g. drugs).
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