New method causes to self-destruct

  |   June 11, 2020

Research led by the Institut de Neurociències (INc-UAB)  has found a new method to battle cancer by inducing potent stress in the tumor using autophagy to cause cell destruction.  The technique has been revealed with the new anti-tumor drug, ABTL0812, that is currently in clinical trials. The findings of the team have shown with samples taken from oncologic patients, and the research study has been published in the journal ‘Autophagy.’ The research, led by scientists from the Institut de Neurociències (INc-UAB), in collaboration with researchers from the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), explains a new approach, through which, the anti-tumor drug ABTL0812  induces stress in tumors and causes cell destruction by cytotoxic autophagy. 

Currently the molecule is being tested in patients diagnosed with advanced endometrial and squamous lung carcinoma, along with the standard chemotherapy. The team’s findings describe a novel strategy to tackle cancer by manipulating dihydroceramide, which is a group of cellular lipids.  For the first time, the researchers have also discussed the  detection of mRNAs of two stress-related proteins, TRIB3 and CHOP, in blood samples of patients undergoing  clinical trials, backing  their use as pharmacodynamic biomarkers. The team examined how the drug ABTL0812 deploys its anti-tumor action. The molecule was developed by AbilityPharma, a biopharmaceutical company based at the UAB Research Park. The company contacted Dr. Jose Miguel Lizcano, the co-ordinator of the study from the INC and the UAB Biochemistry and Molecular Biology Department, to investigate the anti-tumor mechanism undertaken by ABTL0812. Since then, the team has carried out research in the laboratory simultaneously with clinical trials.

Dr. Lizcano says that cancer cell death occurs due to alterations in the levels of cellular dihydroceramide and elevated levels induce severe stress of the endoplasmic reticulum, which results in accumulation of defective proteins. This  causes the cells to activate compensatory response known as Unfolded Protein Response (UPR). This response, Dr. Lizcano explains,  when sustained,  can induce autophagy, ultimately leading to cancer cell death. The researchers believe that this new mechanism could be safely incorporated in the treatment regiments of different types of cancers.

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