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Despite the use of intensive multimodal therapy, metastatic cancer often leads to fatal clinical outcomes. There is a strong need to develop new targeted strategies that inhibit molecules that are important for the development of the tumor. p53 acts as "guardian of the genome", "the guardian of the genome", because of its ability to cause tumor cells to suicide. Because of this property of p53, it is inactivated in the majority of human tumors. Animal model studies have shown that restoration of p53 activity in established tumors leads to their regression. Therefore, p53 is an excellent target for anti-cancer agents. Mutant p53-reactivating molecule APR-246 is currently being tested in Phase Ib / II clinical trials in 8 countries in Europe, the US and Australia, including PiSARRO ovarian cancer trials. We need to better understand which specific molecular mechanisms, in addition to mutant p53, give sensitivity or resistance to this treatment if we are to handle cancer effectively. The main task of P53 is to activate a cellular program that leads to cell death. In our laboratory, we have shown that p53 can also inhibit carcinogenic oncogenes, which cancer cells depend on. But we know very little about the mechanism behind this. Explanation of these mechanisms will enable the development of better strategies for the clinical use of drugs that reactivate p53 and stratification of patients. Our research will also contribute to the development of new prognostic and predictive parameters that improve conventional cancer treatment. Our ambition is to create a clinically relevant model to facilitate the stratification of patients responding to APR-246-based mutant p53 directional therapy, to detect predictive biomarkers and to identify drug combinations for effective treatment and overcoming resistance.

Despite intensive multimodal therapy, metastatic cancer often leads to a fatal clinical outcome. There is a strong need to develop new targeted strategies that inhibit molecules are important for tumor progression. p53 acts as the "guardian of the genome" due to its ability to prevent tumors. Therefore, p53 is a good target for anti-cancer drugs: if we use substances that restore its activity, it will cause tumors to decrease. p53's primary function is to activate a cellular program that leads to cell death. When p53 detects that a cell is damaged and can become a tumor cell, it produces signals that cause the cell to destroy itself. In our laboratory, we have shown that p53 can also suppress the cell's survival program in the tumor, and that this is crucial for its function. But we know very little about the mechanism behind this. In order to effectively use substances that restore p53's function and treat cancer, we must understand the molecular mechanism, that is, exactly how p53 prevents cancer cells from surviving. Our research aims to develop better strategies for the clinical use of substances that reactivate p53. Identification of new factors that are important for p53's function will lead to new targets for anti-cancer drugs. Our research will also contribute to the development of new prognostic and predictive parameters to improve conventional cancer treatment.

Despite intensive multimodal therapy, metastatic cancer often leads to a fatal clinical outcome. There is a strong need to develop new targeted strategies that inhibit molecules are important for tumor progression. p53 acts as the "guardian of the genome" due to its ability to prevent tumors. Therefore, p53 is a good target for anti-cancer drugs: if we use substances that restore its activity, it will cause tumors to decrease. p53's primary function is to activate a cellular program that leads to cell death. When p53 detects that a cell is damaged and can become a tumor cell, it produces signals that cause the cell to destroy itself. In our laboratory, we have shown that p53 can also suppress the cell's survival program in the tumor, and that this is crucial for its function. But we know very little about the mechanism behind this. In order to effectively use substances that restore p53's function and treat cancer, we must understand the molecular mechanism, that is, exactly how p53 prevents cancer cells from surviving. Our research aims to develop better strategies for the clinical use of substances that reactivate p53. Identification of new factors that are important for p53's function will lead to new targets for anti-cancer drugs. Our research will also contribute to the development of new prognostic and predictive parameters to improve conventional cancer treatment.

Despite intensive multimodal therapy, metastatic cancer often leads to a fatal clinical outcome. There is a strong need to develop new targeted strategies that inhibit molecules are important for tumor progression. p53 acts as the "guardian of the genome" due to its ability to prevent tumors. Therefore, p53 is a good target for anti-cancer drugs: if we use substances that restore its activity, it will cause tumors to decrease. p53's primary function is to activate a cellular program that leads to cell death. When p53 detects that a cell is damaged and can become a tumor cell, it produces signals that cause the cell to destroy itself. In our laboratory, we have shown that p53 can also suppress the cell's survival program in the tumor, and that this is crucial for its function. But we know very little about the mechanism behind this. In order to effectively use substances that restore p53's function and treat cancer, we must understand the molecular mechanism, that is, exactly how p53 prevents cancer cells from surviving. Our research aims to develop better strategies for the clinical use of substances that reactivate p53. Identification of new factors that are important for p53's function will lead to new targets for anti-cancer drugs. Our research will also contribute to the development of new prognostic and predictive parameters to improve conventional cancer treatment.

The key to successful cancer treatment is to develop drugs that specifically target important proteins in cancer. The p53 protein is a powerful naturally occurring tumor suppressor that counteracts tumor emergence by programmed cell death (apoptosis). More than 50% of all tumors carry a mutated TP53 gene. In tumors without TP53 mutation, the p53 protein is inactivated due to its accelerated degradation of MDM2. By screening small molecule libraries that can inhibit tumor growth, we have found two substances: PRIMA-1MET / Apr-246 is selective for tumor cells that express mutated p53, and RITA is selective for non-mutated p53 Many genes play a role in the onset of cancer, requiring a cancer treatment to attack multiple targets to ensure that the treatment is successful and to prevent resistance. This project is aimed at identifying new target proteins for combined treatments and developing substances that can counteract two important oncogenes simultaneously. These should also interact with PRIMA-1MET and RITA which reactivate p53. This will reduce the risk of patients developing resistance to cancer drugs. To achieve these goals we will use modern molecular and cell biological methods as well as system biology. The vision is to create new tumor-specific drugs and find drugs that can interact with each other, which will mean that our results can be used more quickly in the healthcare sector and benefit both patients and society.