The U.S. National Cancer Institute (NCI) has initiated a major natural history study involving the collection of tissue samples from a large cohort of patients with various thoracic malignancies, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and thymic epithelial tumors (TET). This research (NCT02146170) aims to prospectively track up to 2,000 patients, systematically collecting blood, urine, and saliva, as well as surgical and biopsy-derived cancer tissues. This goes beyond a simple observational study of patient survival data; it represents a long-term national project by the NCI to comprehensively dissect the entire process of cancer, from its onset and metastasis to the acquisition of resistance, at the molecular level.

The NCI will leverage next-generation sequencing (NGS) technology to analyze the transcriptome, proteome, and epigenetic methylation changes in cancer patients based on the collected bio-samples. This detailed analysis will provide critical foundational data for the future development of companion diagnostics (CDx) and the identification of novel therapeutic targets. For pharmaceutical and biotechnology companies, this database can be utilized in clinical trial design to accurately select patient populations with high drug responsiveness, thereby increasing clinical success rates and significantly reducing the risk of costly clinical failures.

This research bridges the gap between the large global NSCLC market (estimated at up to USD 33 billion by 2025, with PD-1 immune checkpoint inhibitors like Keytruda dominating the standard of care) and the underserved rare cancer market. While the thymic epithelial tumor (TET) and extrapulmonary small cell cancer (ESCC) markets are projected to grow at an annual rate of 7.5%, reaching approximately USD 7 billion by 2033, research investment in these rare diseases remains relatively limited, resulting in significant unmet medical needs. The NCI's study encompasses these often-overlooked rare cancers, which is expected to accelerate the development of orphan drugs and significantly expand public precision medicine infrastructure.

Another innovative aspect of this study is its close integration with a rapid autopsy study (13-C-0131), which involves collecting cancer tissue from multiple metastatic sites shortly after the patient's death. By securing longitudinal samples from pre-treatment biopsies to tissues obtained at the time of drug resistance and post-mortem metastatic tissues, the study can completely track the tumor's evolutionary pathway. This will provide unprecedented data to elucidate the mechanisms by which cancer cells develop resistance to platinum-based chemotherapy or immune-oncology agents, paving the way for the development of next-generation therapies to overcome resistance.