Lung cancer is one of the leading causes of cancer-related mortality worldwide, induced by genetic mutations and various external factors. Non-small cell lung cancer (NSCLC), which comprises the majority of lung cancer cases, is significantly driven by diverse genetic mutations. Consequently, genetic data from lung cancer patients are actively used to identify the causes and factors of lung cancer development and progression, as well as to propose treatment methods.

Protein tyrosine kinase 2 (PTK2) is a non-receptor tyrosine kinase that plays a crucial role in cell migration, survival, proliferation, and interactions with the extracellular matrix. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that regulates cancer cell growth, differentiation, and survival, making it an important therapeutic target in NSCLC. EGFR mutations promote cell proliferation, and EGFR tyrosine kinase inhibitors (TKIs) are used as NSCLC treatments. However, resistance to EGFR TKIs can develop during cancer treatment. Toll-like receptors (TLRs) are essential components of the innate immune system, recognizing pathogen-associated molecular patterns (PAMPs) and promoting immune responses. In the tumor microenvironment, TLRs regulate interactions between immune cells and cancer cells, with some studies suggesting that TLRs can promote cancer cell survival and growth. Despite these findings, research on the regulatory interactions between PTK2, EGFR, and TLRs is limited, and the clinical implications of their expression and interactions on lung cancer patient survival remain unclear.

Our research team utilized genetic data from lung cancer patient-derived tumor and normal tissues to confirm that PTK2 expression significantly impacts lung cancer cell proliferation and tumor formation. Additionally, through gene expression and clinical data analysis, we identified that PTK2 expression in lung cancer cells is associated with the expression of EGFR and TLRs, which correlates with patient survival. To provide scientific evidence for this association, we employed CRISPR-Cas9 gene editing, in vitro cancer progression assays, 3D tumor spheroid assays, and in vivo xenografted NSG mouse assays (Figure 1). The results confirmed that PTK2 regulates lung cancer development and formation mediated by EGFR and TLRs. Furthermore, we validated the efficacy of PTK2 inhibitors in modulating lung cancer development and formation mediated by these pathways. Our findings present a significant milestone for biomarker development targeting EGFR and TLR signaling in future lung cancer treatment strategies, potentially contributing to the establishment of new anticancer treatment strategies in the field of personalized precision medicine.

This research was contributed by Ji-Young Kim (Integrated MS/PhD Program, School of Medicine, Sungkyunkwan University), Ji-Hye Shin (Integrated MS/PhD Program, School of Medicine, Sungkyunkwan University), and Dr. Mi-Jung Kim (School of Medicine, Sungkyunkwan University). The results were published in the renowned international journal "Biomarker Research" (IF: 11.1, JCR CATEGORY in MEDICINE top 7%) in the field of personalized medicine and biomarkers. This research was supported by the Mid-career Researcher Support Program and the Basic Research Laboratory Program.

Article: Kim JY, Shin JH, Kim MJ, Choi B, Kang Y, Choi J, Kim SH, Kwan D, Kim DH, Chun E, Lee KY. PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals. Biomark Res. 2024 May 31;12(1):52

논문명: PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signal. (Biomark Res. 2024 May 31;12(1):52)

Figure 1. PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression