Cancer Therapy Research Articles

Optimizing TIL therapy for uveal melanoma: lessons learned and unlearned from cutaneous melanoma.

Adoptive transfer of tumor infiltrating lymphocytes (TIL-ACT) is a personalized cancer therapy that harnesses the anti-tumor activity of tumor resident T cells through ex vivo activation and expansion. This therapy involves the infusion of a single dose of ex vivo expanded TIL together with high dose IL-2 following a preparative lymphodepleting chemotherapy. The United States Food and Drug Administration approved lifileucel in 2024 as the first autologous TIL product for patients with advanced cutaneous melanoma (CM), adding to the list of approved immunotherapies for this highly immunogenic cancer. However, the role for TIL-ACT in other solid tumors is unclear, especially for poorly immunogenic cancers with low tumor mutational burden. In this review, we describe the historical development of TIL-ACT, summarize the clinical results in advanced CM, and describe the novel application of TIL-ACT to metastatic uveal melanoma (UM), a prototypic immunotherapy-resistant solid tumor. We will highlight key biologic differences between CM and UM, their consequential influence on the manufacturing of UM-specific TIL products, and the development of novel biomarkers for precision TIL-ACT for metastatic UM.

Antitumor immune response elicited by M2 TAM-specific DDS via C-type lectin CD209b using cholesteryl pullulan nanogel as a protein drug carrier.

Many cancer patients develop resistance to immunotherapy, highlighting the urgent need for novel therapeutic strategies. Various factors contribute to tumor resistance to immunotherapy, among which tumor-associated macrophages (TAMs) are critical regulators of tumor sensitivity. Therefore, combining cancer immunotherapies with drug delivery systems (DDSs) targeting TAMs has become an intriguing treatment strategy. However, the target molecules used in DDSs are limited to a few receptors expressed on TAMs. Therefore, the identification of novel target molecules for TAM-specific DDS is urgently needed. The current study evaluated the ability of a cholesteryl pullulan (CHP) nanogel to target TAMs via mDC-SIGN (CD209b). This nanogel encapsulated the cytotoxic protein drug Pseudomonas exotoxin A and was injected into a tumor-bearing mouse model. This treatment significantly reduced the abundance of CD209b-positive M2 TAMs and enhanced antitumor immune responses. Ultimately, tumor growth was suppressed, even in a low-immunogenic tumor model. Hence, CD209b is an effective target molecule for M2 TAM-specific DDSs that can be used to develop novel cancer therapies.

Patient with recurrent grade 4 astrocytoma responding favorably to intranasal delivery of NEO100, highly pure perillyl alcohol: illustrative case.

Better treatments are needed for patients with grade 4 gliomas, especially in the setting of recurrence. The authors are developing NEO100, a clinical-grade version of the natural monoterpene perillyl alcohol, as a cancer therapeutic to be administered via intranasal (IN) delivery to patients with recurrent glioma. A 40-year-old woman was diagnosed with an isocitrate dehydrogenase 1-mutant, CNS WHO grade 4 astrocytoma harboring an unmethylated MGMT promoter. She underwent surgery and standard chemoradiation treatment with temozolomide (TMZ), but after 6 cycles of adjuvant TMZ, the tumor recurred. The patient was started on daily IN NEO100 at 288 mg 4 times a day, administered using a nebulizer and nasal mask. Routine MRI revealed steady tumor regression over the course of 13 months of daily IN NEO100, to the point where the tumor became inconspicuous. There were no serious adverse events, and her quality of life improved and remained high. The authors present a case in which IN cancer therapy with NEO100 was well tolerated and was associated with striking tumor regression, providing further evidence that this novel conceptual approach to cancer therapy might become useful for the improved treatment of recurrent glioma. https://thejns.org/doi/10.3171/CASE24683.

Antigen-Targeting Inserted Nanomicelles Guide Pre-Existing Immunity to Kill Head and Neck Cancer.

A significant challenge in cancer therapy is the identification of suitable targets that are specifically and uniformly expressed across heterogeneous tumors. The efficacy of pre-existing antiviral immunity in tumor treatment is limited by the absence of corresponding targets. This study develops a novel platform of antigen-targeted inserted nanomicelles, preS1 (an antigen of hepatitis B virus)-pHLIP nanomicelles, in which tumor-targeting nanomicelles release antigens that label tumor tissue for pre-existing immunity-mediated lysis in situ. In animal models of head and neck cancers, including head and neck squamous cell carcinoma and anaplastic thyroid cancer, preS1-pHLIP nanomicelles effectively inhibited tumor growth, recurrence, and metastasis in animals pre-immunized with preS1. This therapeutic effect is associated with an increase in the proportion of preS1-specific B cells and activated tumor-specific T cells within the tumor microenvironment. Overall, this work has engineered a nanomicelle that can disguise tumor cells as viruses and achieve tumor killing through the pre-existing antiviral immune response. This strategy presents a novel approach for treating tumors with ambiguous therapeutic target profiles.

NQO1-Responsive Prodrug for in Cellulo Release of Cytochalasin B as Cancer Cell-Targeted Migrastatic.

Migrastatic drugs targeting cell motility and suppressing invasiveness of solid tumors, have the potential to bring about a paradigm shift in the treatment of solid cancer. Cytochalasin B (CB) is a potent migrastatic compound, but its clinical use is limited by poor selectivity. Here, a NQO1-responsive prodrug, BQTML-CB is developed, synthesized in three steps from cytochalasin B derived from Preussia similis G22. BQTML-CB is selectively activated in NQO1-positive cancer cells, releasing active CB. In vitro, BQTML-CB significantly inhibits proliferation and migration in NQO1-positive U-2OS cells, causing actin disruption and cytokinesis abnormalities, while sparing NQO1-negative B16-F1 cells. The prodrug shows reduced effects on human neutrophils, indicating reduced immunosuppressive activity of BQTML-CB compared to CB. Co-culture studies reveal a beneficial bystander effect, as cleaved CB diffused into adjacent NQO1-deficient cells. These findings support BQTML-CB as a cancer-targeted prodrug with selective antiproliferative and migrastatic properties, highlighting the potential of C7-OH-modified cytochalasans in cancer therapy.

Innovative nanodelivery systems for targeted breast cancer therapy: overcoming drug delivery challenges and exploring future perspectives.

Cancer chemotherapy is often limited by insufficient drug targeting, which can cause severe adverse effects on healthy tissues. The advent of nanodelivery systems offers a potential solution to this issue. It intricately enhances drug accumulation in tumor regions, while optimizing drug solubility, ensuring colloidal stability, and promoting cellular uptake, significantly improving the precision and efficacy of treatment, opening a gentler yet more effective new path for cancer therapy. This article begins with the pathogenesis of breast cancer and extends to the current treatment methods and their shortcomings, exploring in-depth the targeting therapeutic effects of five innovative nanodelivery technologies used in the treatment of breast cancer in recent years. Finally, it discusses the potential opportunities and challenges that nanodelivery systems may face in future development.

FGFR4 in endocrine resistance: overexpression and estrogen regulation without direct causative role.

Endocrine therapy resistance is the major challenge of managing patients with estrogen receptor positive (ER+) breast cancer. We previously reported frequent overexpression of FGFR4 in endocrine-resistant cell lines and breast cancers that recurred and metastasized following endocrine therapy, suggesting FGFR4 as a potential driver of endocrine resistance. In this study, we investigated the role of FGFR4 in mediating endocrine resistance and explored the therapeutic potential of targeting FGFR4 in advanced breast cancer. A gene expression signature of FGFR4 activity was examined in ER+breast cancer pre- and post-neoadjuvant endocrine therapy and the association between FGFR4 expression and patient survival was examined. A correlation analysis was used to uncover potential regulators of FGFR4 overexpression. To investigate if FGFR4 is necessary to drive endocrine resistance, we tested response to FGFR4 inhibition in long-term estrogen-deprived (LTED) cells and their paired parental cells. Doxycycline inducible FGFR4 overexpression and knockdown cell models were generated to examine if FGFR4 was sufficient to confer endocrine resistance. Finally, we examined response to FGFR4 monotherapy or combination therapy with fulvestrant in breast cancer cell lines to explore the potential of FGFR4 targeted therapy for advanced breast cancer and assessed the importance of PAM50 subtype in response to FGFR4 inhibition. A FGFR4 activity gene signature was significantly upregulated post-neoadjuvant aromatase inhibitor treatment, and high FGFR4 expression predicted poorer survival in patients with ER+breast cancer. Gene expression association analysis using TCGA, METABRIC, and SCAN-B datasets uncovered ER as the most significant gene negatively correlated with FGFR4 expression. ER negatively regulates FGFR4 expression at both the mRNA and protein level across multiple ER+breast cancer cell lines. Despite robust overexpression of FGFR4, LTED cells did not show enhanced responses to FGFR4 inhibition compared to parental cells. Similarly, FGFR4 overexpression and knockdown did not substantially alter response to endocrine treatment in ER+cell lines, nor did FGFR4 and fulvestrant combination treatment show synergistic effects. The HER2-like subtype of breast cancer showed elevated expression of FGFR4 and an increased response to FGFR4 inhibition relative to other breast cancer subtypes. Despite ER-mediated upregulation of FGFR4 post-endocrine therapy, our study does not support a general role of FGFR4 in mediating endocrine resistance in ER+breast cancer. The significant upregulation of FGFR4 expression in treatment-resistant clinical samples and models following endocrine therapy does not necessarily establish a causal link between the gene and treatment response. Our data suggest that specific genomic backgrounds such as HER2 expression may be required for FGFR4 function in breast cancer and should be further explored.

The Role of HDAC3 in Pulmonary Diseases.

Histone deacetylases (HDACs), a class of enzymes involved in epigenetic modifications, play a pivotal role in modulating chromatin structure and gene expression. Among these, histone deacetylase 3 (HDAC3) has emerged as a key regulator in diverse cellular pathophysiological processes. The remarkable therapeutic potential of HDAC inhibitors in lung cancer has intensified research into the role of HDAC3 in pulmonary diseases. Through deacetylating histones and non-histone proteins, HDAC3 has been increasingly recognized for its critical involvement in regulating inflammatory responses, fibrotic processes, and oncogenic signaling pathways, positioning it as a compelling therapeutic target. This review systematically examines the structural and functional features of HDAC3 and discusses its multifaceted contributions to pulmonary pathologies, including lung injury, pulmonary fibrosis, and lung cancer. Additionally, we critically evaluate advances in HDAC inhibitor-based therapies for lung cancer, with emphasis on the development of HDAC3-targeted therapies. As a promising therapeutic target for pulmonary diseases, HDAC3 needs to be further investigated to elucidate its regulatory mechanisms and facilitate the development of selective inhibitors for clinical translation.

Modifications of RNA in cancer: a comprehensive review.

RNA modifications play essential roles in post-transcriptional gene regulation and have emerged as significant contributors to cancer biology. Major chemical modifications of RNA include N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (ψ), and N7-methylguanosine (m7G). Their dynamic regulation highlights their roles in gene expression modulation, RNA stability, and translation. Advanced high-throughput detection methods, ranging from liquid chromatography-mass spectrometry and high-performance liquid chromatography to next-generation sequencing (NGS) and nanopore direct RNA sequencing, have enabled detailed studies of RNA modifications in cancer cells. Aberrant RNA modifications are associated with the dysregulation of tumor suppressor genes and oncogenes, influencing cancer progression, therapy resistance, and immune evasion. Emerging research suggests the therapeutic potential of targeting RNA-modifying enzymes and their inhibitors in cancer treatment. This review compiles and analyzes the latest findings on RNA modifications, presenting an in-depth discussion of the diverse chemical alterations that occur in RNA and their profound implications in cancer biology. It integrates fundamental principles with cutting-edge research, offering a holistic perspective on how RNA modifications influence gene expression, tumor progression, and therapeutic resistance. It emphasizes the need for further studies to elucidate the complex roles of RNA modifications in cancer, as well as the potential for multimodality therapeutic strategies that exploit the dynamic and reversible nature of these epitranscriptomic marks. It also attempts to highlight the challenges, gaps, and limitations of RNA modifications in cancer that should be tackled before their functional implications. Understanding the interplay between RNA modifications, cancer pathways, and their inhibitors will be crucial for developing promising RNA-based therapeutic approaches to cancer and personalized medicine strategies.

Nanomedicine innovations in colon and rectal cancer: advances in targeted drug and gene delivery systems.

Nanotechnology has revolutionized cancer diagnostics and therapy, offering unprecedented possibilities to overcome the constraints of conventional treatments. This study provides a detailed overview of the current progress and difficulties in the creation of nanostructured materials, with a specific emphasis on their use in drug and gene delivery systems. The study examines tactics that attempt to improve the effectiveness and safety of chemotherapeutic drugs such as doxorubicin (Dox) by focusing on the potential of antibody-drug conjugates and functionalized nanoparticles. Moreover, it clarifies the challenges encountered in administering nanoparticles orally for gastrointestinal treatments, emphasizing the crucial physicochemical properties that affect their behavior in the gastrointestinal system. This study highlights the transformational potential of nanostructured materials in precision oncology by examining advanced breakthroughs such cell membrane-camouflaged nanoparticles and inorganic nanoparticles designed for gastrointestinal disorders. The text investigates the processes involved in the absorption of nanoparticles and their destruction in lysosomes, revealing the many methods in which enterocytes take up these particles. This study strongly supports the use of advanced nanoparticle-based methods to reduce the harmful effects on the whole body and improve the effectiveness of therapy, based on a thorough examination of current experiments on animals and humans. The main objective of this paper is to provide a fundamental comprehension that will stimulate more investigation and practical use in the field of cancer nanomedicine, advancing its boundaries.

Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies

Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies

Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy

A sustained blood supply is critical for tumor growth, as it delivers the nutrients and oxygen required for development. Targeting of blood vessel formation via immunotherapies is an area of great importance. Knowing that certain embryonic genes, such as carcinoembryonic antigens (CEA) and oncofetal fibronectin, become reexpressed in malignant transformation, we hypothesized that a similar phenomenon holds true for tumor endothelial cells (TECs) as well. An approach for identification of highly selective tumor endothelial markers was conducted to develop targeted antiangiogenic immunotherapies. We first queried the transcriptome that is present during embryo development. We then performed a systematic search for genes selectively expressed in the mouse embryo at days E11 and E18, as compared to the transcriptome of the adult mouse. Subsequently, we queried for expression of these embryonic genes in sorted murine TECs. This approach identified among others the tumor endothelial antigens fibrillin-2 (Fbn2), elastin microfibril interface-located protein 2 (Emilin2) as well as the tumor endothelial antigens lysyl oxidase (Lox) and serine/cysteine protease inhibitor, clade E, member 1 (Serpine1; Pai-1). For these selected genes, functional involvement in angiogenesis was confirmed in in vitro bioassays. We subsequently used iBoost conjugate vaccine technology to develop vaccines against the selected targets. For all four targets, vaccination readily induced target-specific antibody responses in mice, resulting in inhibition of tumor growth. Access to highly specific tumor endothelial markers provides opportunities for direct targeting of the tumor vasculature with high specificity, without affecting healthy vasculature.

Automated fast-flow synthesis of the immune checkpoint receptors PD-1 and PD-L1.

Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are key targets for cancer therapy. Here, we use automated fast-flow peptide synthesis (AFPS) to rapidly produce these challenging β-sheet-rich proteins in their active forms following oxidative refolding protocols. The methods presented here provide rapid access to synthetic, air-stable mutants of PD-1 and PD-L1 in which L-methionine residues are substituted with L-norleucine, potentially enabling investigation of post-translational modifications and mirror-image analogs for drug discovery.

Lnc-TPT1-AS1/CBP/ATIC Axis Mediated Purine Metabolism Activation Promotes Breast Cancer Progression.

The purine biosynthetic pathway was recently identified to play a crucial role in breast cancer progression. However, little was known about the regulatory mechanisms of long non-coding RNA in breast cancer purine metabolism. In this study, we discovered that LncRNA TPT1-AS1 (TPT1-AS1) was downregulated in breast cancer tissues. Its introduction in breast cancer cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis suggested that the purine biosynthetic pathway was activated in TPT1-AS1-knockdown MCF-7 cells. Inosine monophosphate (IMP), the product of de novo purine biosynthesis, was significantly upregulated. Mechanistically, we found that TPT1-AS1 could physically interact with CBP (CREB-binding protein), which consequently led to the loss of H3K27Ac in the promoter area of ATIC, the key enzyme of IMP synthesis. This process could block breast cancer purine metabolism and inhibit breast cancer progression. In conclusion, our findings illustrate the role of non-coding RNAs in breast cancer purine metabolism reprogramming and present a potential candidate for breast cancer therapy.

Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy.

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is effective in B cell malignancies. However, the persistence of cancer cells with low levels or complete absence of the target antigen, thereby evading detection by CAR T cells, leads to relapse. These evasion mechanisms highlight the need for receptors with enhanced sensitivity and multispecificity. We introduce a synthetic chimeric T cell receptor (ChTCR) that confers superior antigen sensitivity compared with CARS and previous hybrid TCR designs and is readily adapted for bispecific targeting. ChTCRs replicate the structure of natural TCRs, form classical immune synapses and demonstrate TCR-like signaling. T cells expressing bispecific ChTCRs (Bi-ChTCRs) are more effective than bispecific CAR T cells in eradicating tumors with heterogeneous antigen expression in vivo in female mice. The Bi-ChTCR architecture is resilient and can be designed to target pairs of B cell and multiple myeloma antigens. These findings provide a widely applicable strategy to combat tumor heterogeneity and prevent relapse.

The synergistic antitumour effect of Carrimycin combined with 5-fluorouracil on colorectal cancer

5-Fluorouracil (5-FU)-based chemotherapy often leads to drug resistance and adverse reactions in individuals with colorectal cancer (CRC). Carrimycin (CAM), a drug with notable antitumour effects across various tumour types, including hepatocellular carcinoma, glioblastoma, and small-cell lung carcinoma, offers an alternative owing to its limited side effects. Combination therapy is a common strategy to mitigate the negative effects of 5-FU and enhance its therapeutic efficacy. This study aimed to investigate the potential synergistic antitumour effects of CAM and 5-FU on HCT-15 and HT-29 CRC cell lines. Using computational analysis, we identified and quantified the synergistic effects of CAM and 5-FU. The combination therapy significantly outperformed 5-FU alone in inhibiting cell proliferation, colony formation, cell cycle progression, and migration. Additionally, it markedly increased the levels of reactive oxygen species and induced DNA damage. Furthermore, RNA-seq analysis revealed that the JNK and p38 MAPK signalling pathways were activated by this combination. In addition, the synergistic effects of the combination therapy were validated in a mouse subcutaneous tumour graft model. In conclusion, CAM enhances the sensitivity of CRC cells to 5-FU both in vitro and in vivo, suggesting its potential as a promising candidate for combination cancer therapy.

Loss of Golga7 Suppresses Oncogenic Nras-Driven Leukemogenesis without Detectable Toxicity in Adult Mice.

NRAS mutations are prevalent in human hematological malignancies and are also common in certain solid tumors, including melanoma and colon cancer. Despite their crucial role in oncogenesis, no effective therapies targeting NRAS have been developed. Inhibiting NRAS localization to the plasma membrane (PM) represents a promising strategy for cancer therapy, as its oncogenic signaling relies on PM localization. Knocking out Golgin subfamily A member 7 (Golga7), an accessory protein of RAS palmitoyltransferases, through a conditional gene editing approach drastically suppresses the development of myeloid leukemia induced by the activation of NrasG12D/G12D knock-in alleles in mice. The loss of Golga7 disrupts NRASG12D PM localization in bone marrow cells without altering the level of NRASG12D palmitoylation. Notably, Golga7 is dispensable for normal hematopoiesis in adult mice. While constitutive Golga7 knockout leads to embryonic lethality, the ubiquitous knockout of Golga7 induced in adult mice does not manifest any measurable toxic effects. These findings indicate that GOLGA7 is an effective and safe therapeutic target for NRAS-driven leukemias.

Aggregation induced emission luminogen bacteria hybrid bionic robot for multimodal phototheranostics and immunotherapy

Multimodal phototheranostics utilizing single molecules offer a “one-and-done” approach, presenting a convenient and effective strategy for cancer therapy. However, therapies based on conventional photosensitizers often suffer from limitations such as a single photosensitizing mechanism, restricted tumor penetration and retention, and the requirement for multiple irradiations, which significantly constrain their application. In this report, we present an aggregation-induced emission luminogen (AIEgen) bacteria hybrid bionic robot to address above issues. This bionic robot is composed of multifunctional AIEgen (INX-2) and Escherichia coli Nissle 1917 (EcN), i.e., EcN@INX-2. The EcN@INX-2 bionic robot exhibits near-infrared II (NIR-II) fluorescence emission and demonstrates efficient photodynamic and photothermal effects, as well as tumor-targeting capabilities. These features are facilitated by the complementary roles of INX-2 and EcN. The robot successfully enables in vivo multimodal imaging and therapy of colon cancer models in female mice through various mechanisms, including the activation of anti-tumor immunity, as well as photodynamic and photothermal therapy. Our study paves an avenue for designing multifunctional diagnostic agents for targeted colon cancer therapy through image-guided combinational immunotherapy.

Injectable 2D-MoS2-integrated Bioadhesive Hydrogel as Photothermal-Derived and Drug-Delivery Implant for Colorectal Cancer Therapy.

Photothermal therapy (PTT) combined with chemotherapy using hydrogel as a delivery platform is considered a promising strategy for the treatment of advanced colorectal cancer (CRC). However, maintaining the stability of photo-absorbing agents (PTA) in the hydrogel and ensuring that the hydrogel remains anchored to the tumor tissue presents significant challenges. Herein, this work introduces an injectable 2D molybdenum disulfide (2D-MoS2)-integrated adhesive hydrogel, specifically N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitro-sophenoxy) butanamide-linked sodium alginate-MoS2-5-fluorouracil (AlgNB/MoS2/5-FU). This hydrogel functions as a near-infrared light (NIR)-triggered photothermal and drug-delivery implant for CRC treatment. The MoS2 nanosheets maintain superior dispersibility in the hydrogel and exhibit a highly efficient NIR-triggered photothermal effect. Importantly, the aldehyde group in AlgNB also imparted tissue adhesion to the hydrogel, the adhesive hydrogel is used to infiltrate and anchor within tumor tissue. The injectable adhesive AlgNB/MoS2/5-FU hydrogel shows remarkable efficacy in inhibiting SW480 cells proliferation and promoting colorectal tumor regression by triggering PTT and delivering the 5-FU drug in both in vitro and in vivo studies. The potential synergistic mechanism of PTT and 5-FU chemotherapy may contribute to inhibiting DNA repair and enhancing a robust immune response. Therefore, this research provides valuable strategic insights for the synergistic treatment of localized CRC.

Research trends of neoadjuvant therapy in lung cancer: a bibliometric analysis

BackgroundLung cancer is the most prevalent malignancy worldwide. Only a fraction of early-stage patients undergo radical surgery; however, many still experience recurrence and metastasis within 5 years postoperatively (approximately 30–75%). Neoadjuvant therapy has revolutionized the treatment approach for lung cancer, with a growing number of clinical trials investigating this modality. This study provides a comprehensive analysis of neoadjuvant therapy in lung cancer, intending to guide future research.MethodTo extract literature on neoadjuvant therapy for lung cancer published in the Web of Science Core Collection, spanning January 1, 2004, to December 31, 2023. Utilizing software tools including VOSviewer, CiteSpace, and GraphPad Prism to conduct bibliometric analysis and visualization studies on countries, institutions, journals, authors, co-cited references, and keywords in this field.ResultsA sum of 6,085 research publications from 84 countries were analyzed, with the United States leading in publications on neoadjuvant therapy for lung cancer. The institution that publishes the most articles is the University of Texas System. The most published journal is Annals of Thoracic Surgery, while the most frequently co-cited journal is Journal of Clinical Oncology. Eight of the top ten co-cited references concern immune checkpoint inhibitors(ICIs). Keyword burst analysis indicates that the current research focuses and trends mainly center around four areas: ICIs, clinical trials, efficacy, and non-small cell lung cancer (NSCLC).ConclusionsThis is the first bibliometric study of neoadjuvant therapy in lung cancer. Over the past two decades, interest in this field has steadily increased, particularly since 2017. The United States is the largest contributor and has the highest number of publications in this field. Immune checkpoint inhibitors, clinical trials, efficacy, and NSCLC are hotspots in neoadjuvant therapy for lung cancer, both now and in the foreseeable future.