Year: 2024
Type: dissertation
Abstract: Without balance there is no harmony.In an organism, cell life and cell death are integral components of its life cycle. The precise regulation of these two interconnected processes is crucial to maintain the proper balance and functionality of living organisms. Just like cell division and energy production, cell death is a natural and essential process in the life cycle of cells. It plays a crucial role in a variety of physiological and developmental processes in multicellular organisms (e.g., embryonal development and immune selection of B and T cells). Its action makes it possible to sculpt organs, repair and/or protect tissues. Cell death mechanisms are found early in evolution from the simplest multicellular organisms. Understanding the mechanisms of cell death is crucial for both normal physiological processes and the development of diseases. Dysregulation of cell death can contribute to various pathological conditions, including cancer, neurodegenerative disorders, and autoimmune diseases. Researchers and medical professionals continue to study these processes to develop therapeutic strategies targeting cell death pathways.Despite all scientific progress, genetic advances and ongoing therapeutic trials, cancer remains the leading cause of premature death before the age of 65 in both men and women. In recent years, new types of anti-cancer drugs have been developed: unlike the widely active toxic chemicals known as cytotoxic chemotherapy, these new drugs are based on a better understanding of the signaling pathways in the tumor cell, avoiding thus the indiscriminate destruction of normal cells. These drugs were labeled “targeted therapies”. Much progress has been made with targeted therapies in a limited number of indications, but efforts are still needed to validate new pathways as therapeutic targets. The new agents will be used alone or in most cases in combination with pre- existing therapies. The majority of the targeted molecules currently under development focus on tyrosine kinase-dependent signaling pathways and target receptors involved in angiogenesis such as EGFR and VEGFR. In contrast, the smaller fraction of these molecules primarily comprises a restricted set of agents that target novel cell signaling pathways in the context of cancer.Obviously, in oncology, scientists and the pharmaceutical industries have been largely interested in exploring the induction of cell death in cancer cells, primarily through the conventional death pathways. Despite the progress that has been achieved thanks to targeted therapies, efforts remain to be made to validate new pathways as therapeutic targets. Several families of receptors have thus been studied, especially the members of the TRAIL families. However, there has been little success so far in terms of approved agents.In this project, we will focus on a different, innovative and very original technique to better understand the apoptotic pathway induced by the dependence receptor UNC5B which binds to netrin-1.
Source: HAL
Author: Karam, Nathalie
Institution: Lyon 1 Université
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4401159162