February 23, 2023

Spatially-resolved Molecular Characterization of Cancer Cell Plasticity to Empower Detection and Prediction of Human Lung Adenocarcinoma Progression

7th Call, iPostdoc

Short Summary

In lung adenocarcinoma, the most common form of lung cancer, aggressive cellular states can emerge in different parts of the tumor, increasing its capability to invade nearby tissues and metastasize to distant organs. In this project, we aim at characterizing these aggressive states, understanding how they are spatially organized in the tumor, and using this knowledge to develop a digital pathology approach that provides an augmented view of the disease progression to use in clinical practice.

Goals

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.

Significance

When a lung adenocarcinoma is surgically resected, pathologists observe its morphologic features under a microscope to predict its prognosis and likelihood of recurrence and metastasis. With this study, we aim at providing an augmented view of the disease status and future development that might improve these predictions and inform novel therapeutic approaches aimed at arresting and reversing lung adenocarcinoma progression.

Background

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.