In this project, we first aim at deciphering the emergence of aggressive cellular states resulting from plastic transitions during lung adenocarcinoma progression. Next, we will study how these cellular states are spatially organized in the tumor, and how do they interact with the immune cells surrounding and infiltrating them. Finally, we will develop a ‘digital pathology’ approach aimed at detecting and visualizing the aggressive cellular states from a tumor specimen, providing an augmented view of the disease progression that could inform the personalized clinical management of the patient.
Lung adenocarcinoma, the most common form of lung cancer, is the greatest cause of cancer-related deaths worldwide. It arises when the DNA of a normal lung epithelial cell is hit by multiple tumorigenic mutations, often as a result of tobacco smoking, which transforms and proliferates in an uncontrolled manner. As it progresses, the malignant mass acquires the capability to invade nearby tissues and ultimately to metastasize to distant organs, severely threatening the survival of the patient. This progression does not necessarily require new mutations, but can also occur through other alterations that affect the biological functions of the cancer cells without changing their DNA. This dynamic and continuous process is termed ‘cancer cell plasticity’. Plastic transitions can thus give rise to various cellular states in different regions of the tumor, some of which will be more aggressive and likely to originate metastasis. An early detection of these life-threatening cellular states might improve the clinical management and prognosis of patients, and could potentially lead to new therapeutic approaches.
