Gene expression profile comparisons of the immune population and the tumor subtypes in pre and post immune checkpoint inhibition (ICI) /chemo combination therapies in small cell lung cancer (SCLC)

Lung cancer is divided into two main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC comprises about 15% of lung cancers. It is usually caused by smoking and is a very aggressive and fatal cancer that is diagnosed in about 30,000 to 35,000 patients every year in the US. Even with currently updated treatments that include immunotherapies, almost half of the patients with SCLC die of their tumor within a year of diagnosis. Therefore, finding new and more durable therapies for SCLC is extremely urgent. Patients with SCLC almost always respond to the initial treatments which includes combinations of chemotherapy (drugs that kill cancer cells by damaging their genetic material) and immune therapies (drugs that mobilize the body's own immune system to attack the cancer cells), such as immune checkpoint inhibition. However, almost universally these patients’ cancer comes back in a much more treatment-resistant form. To find new therapies, it is crucial to understand the important features of the recurred SCLC tumors (rSCLC - where the cancer has come back) in comparison with the more treatment sensitive SCLC tumors at the initial time of diagnosis (iSCLC, for initially diagnosed SCLC).
The goal of this study is to compare the genomic profiles of rSCLC tumors against iSCLC tumors. These comparisons will be at the level of gene expression which is a type of genomic data. A gene is a basic unit of heredity. It's a specific sequence of DNA. Gene expression is the process by which the information encoded in a gene is turned into a function. We have chosen this method because gene expression is one of the most informative types of genomic data for explaining two important aspects of tumor biology including (i) tumor abnormalities that promote specific molecular signaling that promote cancer. Molecular signaling (also known as cell signaling) refers to processes through which cells send and receive chemical signals to and from their environment or other cells. These signals act as messengers and trigger various processes such as cellular growth, proliferation, progression and cell death. Specific signaling processes that promote cancer development and progression are known as “oncogenic signaling”. (ii) increased concentration (enrichments) or decreased concentration (depletions) of specific immune cells that are known for their functions either in promoting or fighting against cancer within the tumor area. We anticipate that discovering newly activated oncogenic signaling and specific changes in immune cell populations in the rSCLC after initial treatments will provide crucial clues for designing more effective treatment strategies for the treatments of all SCLC.