The development and growth of tumors remains an important and ongoing threat to human life around the world. While advanced therapeutic strategies such as immune checkpoint therapy and CAR-T have achieved astonishing progress in the treatment of both solid and hematological malignancies, the malignant initiation and progression of cancer remains a controversial issue, and further research is urgently required. The experimental animal model not only has great advantages in simulating the occurrence, development, and malignant transformation mechanisms of tumors, but also can be used to evaluate the therapeutic effects of a diverse array of clinical interventions, gradually becoming an indispensable method for cancer research. In this paper, we have reviewed recent research progress in relation to mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, to help guide the future study of malignant mechanisms and tumor prevention.

Lung adenocarcinoma is the most prevalent type of lung cancer, with invasive lung adenocarcinoma being the most common subtype. Screening and early treatment of high-risk individuals have improved survival; however, significant differences in prognosis still exist among patients at the same stage, especially in the early stages. Invasive lung adenocarcinoma has different histological morphologies and biological characteristics that can distinguish its prognosis. Notably, several studies have found that the pathological subtypes of invasive lung adenocarcinoma are closely associated with clinical treatment. This review summarised the distribution of various pathological subtypes of invasive lung adenocarcinoma in the population and their relationship with sex, smoking, imaging features, and other histological characteristics. We comprehensively analysed the genetic characteristics and biomarkers of the different pathological subtypes of invasive lung adenocarcinoma. Understanding the interaction between the pathological subtypes of invasive lung adenocarcinoma and the tumour microenvironment helps to reveal new therapeutic targets for lung adenocarcinoma. We also extensively reviewed the prognosis of various pathological subtypes and their effects on selecting surgical methods and adjuvant therapy and explored future treatment strategies.

Cancer remains a serious social health problem, and immunotherapy has become the major treatments in tumor treatment. Additionally, improving the efficiency and safety of treatment is necessary. Further, more therapy targets are warranted for future tumor treatments. In this review, in addition to examining the currently recognized role of immune regulation, we focus on the proliferative role of 15 immune checkpoints in various tumors, including PD1, PD-L1, FGL1, CD155, CD47, SIRPα, CD276, IDO1, SIGLEC-15, TIM3, Galectin-9, CD70, CD27, 4-1BBL, and HVEM. We managed to conclude that various immune checkpoints such as PD1/PD-L1, FGL1, CD155, CD47/SIRPα, CD276, and SIGLEC-15 all regulate the cell cycle, and specifically through Cyclin D1 regulation. Furthermore, a variety of signal pathways engage in proliferation regulation, such as P13K, AKT, mTOR, and NK-κB, which are also the most common pathways involved in the regulation of immune checkpoint proliferation. Currently, only PD1/PD-L1, CD47/SIRPα, TIM3/Galectin-9, and CD70/CD27 checkpoints have been shown to interact with each other to regulate tumor proliferation in pairs. However, for other immune checkpoints, the role of their receptors or ligands in tumor proliferation regulation is still unknown, and we consider the enormous potential in this area. An increasing number of studies have validated the various role of immune checkpoints in tumors, and based on this literature review, we found that most of the immune checkpoints play a dual regulatory role in immunity and proliferation. Therefore, the related pathways in proliferation regulation can served the role of therapy targets in tumor therapy. Further, great potential is displayed by IDO1, SIGLEC-15, 4-1BBL, and HVEM in tumor proliferation regulation, which may become novel therapy targets in tumor treatment.

Background: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. Methods: Publicly available datasets were used for differential gene expression and immune infiltration analyses, and their correlation with patient survival. A total of 322 ESCA and 161 paracancer samples were collected and evaluated by performing immunohistochemistry and the H score was obtained by performing semiquantitative analysis. In vitro transfection of ESCA cell lines with lentivirus vectors targeting CD155 was performed to knockdown the protein. These cells were analyzed by conducting RNA sequencing, and the effects of CD155 knockdown on cell cycle and apoptosis were verified with flow cytometry and Western blotting. In addition, in vivo experiments using these engineered cell lines were performed to determine the role of CD155 in tumor formation. A small interfering RNA-mediated knockdown of Nectin3 was used to determine whether it phenocopied the profile of CD155 knockdown. Results: CD155 is highly expressed in ESCA tissues and is positively associated with PD1, PDL1, CD4, IL2RA, and S100A9 expression. Furthermore, CD155 knockdown inhibited ESCA cells’ proliferation by impairing the cell cycle and inducing cell apoptosis. Bioinformatics analysis of the gene expression profile of these engineered cells showed that CD155 mainly contributed to the regulation of PI3K/Akt and MAPK signals. The downregulation of Nectin3 expression phenocopied the profile of CD155 knockdown. Discussion: CD155 may cooperate with PD-1/PD-L1 to support ESCA proliferation in ways other than regulating its underlying immune mechanisms. Indeed, CD155 downregulation can impair ESCA cell pro-cancerous behavior via the inhibition of the PI3K/Akt and MAPK signaling pathways. Moreover, Nectin3 may be a ligand of CD155 and participate in the regulation of ESCA cells’ proliferation. Hence, the inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA.

This study aimed to investigate TCF19's role in lung cancer development, specifically its involvement in the RAF/MEK/ERK signaling pathway. Lung cancer tissue analysis revealed significant TCF19 overexpression. In vitro experiments using A549 and Hop62 cells with TCF19 overexpression demonstrated enhanced cell growth. Transgenic mouse models confirmed TCF19's role in primary tumor development. Transcriptome sequencing identified altered gene expression profiles, linking TCF19 to RAF/MEK/ERK pathway activation. Functional assays elucidated underlying mechanisms, revealing increased phosphorylation of Raf1, MEK1/2, and ERK1/2. Inhibiting RAF1 or ERK through shRaf1 or ERK inhibitor reduced cell cycle-related proteins and inhibited TCF19-overexpressing cell growth. TCF19 was identified as an oncogene in lung carcinoma, specifically impacting the RAF/MEK/ERK pathway. Elevated TCF19 levels in lung cancer suggest targeting TCF19 or its associated pathways as a promising strategy for disease management. This study unveils TCF19's oncogenic role in lung cancer, emphasizing its modulation of the RAF/MEK/ERK pathway and presenting a potential therapeutic target for TCF19-overexpressing lung cancers.

Background and Objective: Pulmonary nodules (PNs) are small (≤3 cm) radiographic opacities within lung parenchyma. The use of low-dose computed tomography (LDCT) has led to a significant increase in the identification of solitary nodules. Malignant lung nodules comprise only 5% of all nodules, with management differing greatly from benign cases. Despite diagnostic advancements, there is heterogeneity in prognosis, which can result in undertreatment of high-risk patients and inappropriate treatment for low-risk patients. Therefore, accurately distinguishing benign from malignant nodules and effectively stratifying the risk of malignant nodules is a pressing clinical challenge requiring urgent resolution. The main objectives of this review were to explore the research progress in the clinical management of malignant PNs, including early detection, individualized treatment, and prognosis prediction, in order to shed light on precision medicine for patients with PNs. Methods: The review examined various approaches for the identification and prognosis prediction of early lung cancer characterized by lung nodules, including the use of classical clinicopathological features, liquid biopsy, and artificial intelligence. Key Content and Findings: The detection rate of early lung cancer characterized by lung nodules is increasing annually, and accurate identification and prognosis prediction are critical for appropriate therapeutic strategies and precise postoperative management. Classical clinicopathological features, such as demographic and radiological features, play an important role in the diagnosis and prognosis assessment of early lung cancer, but liquid biopsy and artificial intelligence are also promising due to their obvious convenience and accuracy. Conclusions: The review highlights the importance of precision medicine in the clinical management of malignant lung nodules. The use of classical clinicopathological features, liquid biopsy, and artificial intelligence can contribute to the early detection, individualized treatment, and accurate prognosis prediction for patients with lung nodules, ultimately improving their clinical outcomes.