Periodic Reporting for period 1 - StemTarget (Development of new therapeutic treatments targeting cancer stem cells.)
Periodo di rendicontazione: 2021-04-01 al 2023-03-31
The last decades of research in oncology have demonstrated the existence of a distinct population of tumor cells, named cancer stem cells (CSC) with a central role in tumor spread and drug resistance. Inside the tumor cell population, some cancer cells are called “differentiated cells” and express specific cellular and molecular biomarkers associated with differentiation, while other cells are more immature and present some other distinct features. These cells are also known as “cancer stem cells”. This Skłodowska-Curie Action “Development of new therapeutic treatments targeting cancer stem cells” looks at how trigger this specific population of cancer cells, and how to conceive new anti-cancer drugs.
Acute myeloid leukemia (AML) accounts for 30% of leukemia in adults. This blood cancer affects nearly 18,000 new people each year in Europe. It is characterized by an excessive and continuous production of abnormal and immature blood cells within the bone marrow and the blood circulation. Intensive chemotherapies currently in use, however, fail to eradicate leukemic stem cells. These dormant cells do not divide but remain a constant threat for the patients. Indeed, even if they are quiescent cells, they are able to wake up and can be responsible of cancer relapse. They can cause leukemia to progress to a more aggressive or to an anti-cancer treatment-resistant form. Destroying these cancer stem cells is therefore the main objective of this project.
The objectives of this project are to (a) collaborate with medical chemists to design new molecules; (b) test all the synthetic compounds in vitro for anti-cancer capacity and toxicity, and (c) develop a platform for drug discovery. A parallel goal of the MSCA Individual Fellowship is also to foster the development of the individual researcher. It would bridge academy with industry and will bring invaluable complementary scientific and soft skills to a researcher with an ideal background in drug development.
Acute myeloid leukemia (AML) accounts for 30% of leukemia in adults. This blood cancer affects nearly 18,000 new people each year in Europe. It is characterized by an excessive and continuous production of abnormal and immature blood cells within the bone marrow and the blood circulation. Intensive chemotherapies currently in use, however, fail to eradicate leukemic stem cells. These dormant cells do not divide but remain a constant threat for the patients. Indeed, even if they are quiescent cells, they are able to wake up and can be responsible of cancer relapse. They can cause leukemia to progress to a more aggressive or to an anti-cancer treatment-resistant form. Destroying these cancer stem cells is therefore the main objective of this project.
The objectives of this project are to (a) collaborate with medical chemists to design new molecules; (b) test all the synthetic compounds in vitro for anti-cancer capacity and toxicity, and (c) develop a platform for drug discovery. A parallel goal of the MSCA Individual Fellowship is also to foster the development of the individual researcher. It would bridge academy with industry and will bring invaluable complementary scientific and soft skills to a researcher with an ideal background in drug development.
The work was conducted through 6 work packages (WPs). WP1 included a discovery phase where 263 molecules were tested for their impact on cell viability. WP2 sought to confirm the anti-leukemic activity of the selected molecules. In WP3, a list of 5 synthetic molecules with a potent effect on cancer cells without toxic side effects on normal blood cells was delivered. WP4 consisted in developing a drug discovery platform for cancer cells. The project was managed under WP5. During the grant, a patent application covering the best new chemical entities was completed with the help of the technology transfer office and a patent attorney. A manuscript describing the steps of the clinical study is in advanced stages of drafting. In WP6, for researcher training and transfer-of-knowledge, the fellow participated in training workshops and multi-day conferences. To transfer of knowledge, a strong relationship with a high school was established with lectures and workshops. Results were also informally disseminated within the research community and supervision/mentoring of early career researchers was provided by the researcher at the lab.
Within the framework of the project, several state-of-the-art research techniques related to the launch of a drug discovery platform from suspension to adherent cells were optimized. The results represent a comprehensive preclinical study with in vitro, ex vivo, and in vivo experiments. The finding that targeting cancer stem cells can work in leukemia as well as in other solid tumors is a promising research avenue for future therapeutic drug development strategies. Given the high incidence of leukemia in our society and the immense challenge of chemoresistance and relapse, this research could provide a significant societal benefit.