Progress towards non-small-cell lung cancer models that represent clinical evolutionary trajectories

Abstract

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although advances are being made towards earlier detection and the development of impactful targeted therapies and immunotherapies, the 5-year survival of patients with advanced disease is still below 20%. Effective cancer research relies on pre-clinical model systems that accurately reflect the evolutionary course of disease progression and mimic patient responses to therapy. Here, we review pre-clinical models, including genetically engineered mouse models and patient-derived materials, such as cell lines, primary cell cultures, explant cultures and xenografts, that are currently being used to interrogate NSCLC evolution from pre-invasive disease through locally invasive cancer to the metastatic colonization of distant organ sites.

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

“…In oncology, studies on human tumor biopsies derived from cancers such as NSCLC, have been limited in particular by a limited access to samples of sufficient sizes and, hence, the difficulty to perform in vitro functional studies with cells derived from these biopsies. To circumvent this bottleneck, one can take advantage of the technical advancements that have included i) the establishment of cell lines (a large majority being of human origin), ii) the use of primary cell cultures, and iii) the development of various mouse models (as illustrated in ( 81 ) for NSCLC).…”

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

“…A faithful recapitulation of inter- and intra-tumor heterogeneity within the TME is key for precision medicine and is often not replicated in other organotypic models ( 13 ). Longevity of the various components which comprise the TME (including immune cells, stromal cells, and tumor cells), ex vitro , is an important consideration when utilizing these models to investigate adjuvant and neoadjuvant treatments ( 14 ).…”

“…An intact TME allows for metabolically active tumor, stromal and immune cells, preserving their native cellular interactions ( 14 ). Consequently, PDEs may more closely reflect responses to SOC and molecularly determined therapeutics compared to other patient-derived models such as cell lines, tumoroids/organoids, or patient-derived xenografts (PDX).…”

Artificial Intelligence-based Tumor Segmentation in Mouse Models of Lung Adenocarcinoma

“…GEMMs in pre-clinical studies provide researchers with opportunities to study tumor microenvironment, isolate and control genetic mutations, determine the therapeutic dosage, and observe host immune response. 3 The most common mutations in human LUAD are activating point mutations in KRAS and inactivation of P53 . 4 , 5 Mice with conditional KRAS activation and P53 loss of function (KP mice) are infected with Cre expressing adenovirus, which activates the transcription of mutant KRAS and loss of P53 .…”