Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X. The patient achieved partial response with afatinib for 17 months. Our case highlights the importance of EGFR mutations in the precision targeted treatment of SMARCA4-dNSCLC.
Humans ; Afatinib/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; DNA Helicases/genetics* ; ErbB Receptors/genetics* ; Lung Neoplasms/pathology* ; Mutation ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Chemotherapy-induced nausea and vomiting (CINV) is common in patients receiving moderately or highly emetogenic chemotherapy and is caused by the activation of peripheral and central nervous system pathways, with the neurokinin-1 receptor playing a central role in delayed CINV. Neurokinin-1 receptor antagonists (NK1RAs) in combination with other antiemetic agents are recommended in international and Chinese guidelines for the prevention of acute and delayed CINV. Therefore, a summary of current data for NK1RAs would be of great clinical utility. This article summarizes the available clinical and real-world data on the use of NK1RAs in CINV prophylaxis, with a focus on evidence from China, where three NK1RAs, aprepitant, fosaprepitant and netupitant, are currently approved. NK1RAs have demonstrated efficacy and favorable safety in the prevention of acute and delayed CINV. Further research is required to determine the optimal use of these drugs and to identify strategies for CINV management in specific patient populations.
Humans ; Vomiting/prevention & control* ; Neurokinin-1 Receptor Antagonists/therapeutic use* ; Nausea/prevention & control* ; Antiemetics/therapeutic use* ; Antineoplastic Agents/adverse effects* ; Aprepitant/therapeutic use* ; Morpholines/therapeutic use*

Glioma, the most prevalent primary tumor of the central nervous system (CNS), is also the most lethal primary malignant tumor. Currently, there are limited chemotherapeutics available for glioma treatment, necessitating further research to identify and develop new chemotherapeutic agents. A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products (NPs) and optimizing their structures. Additionally, targeted drug delivery systems (TDDSs) are employed to enhance drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can penetrate deep into the brain, increase drug concentration and retention time in the CNS, and improve the targeting efficiency of NPs, thereby reducing adverse effects and enhancing anti-glioma efficacy. This paper reviews the research progress of anti-glioma activities of NPs, including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones, and their synthetic derivatives over the past decade. The review also summarizes anti-glioma mechanisms, such as suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversal of immunosuppression. Furthermore, the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined. The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
Humans ; Glioma/metabolism* ; Biological Products/therapeutic use* ; Animals ; Brain Neoplasms/genetics* ; Drug Delivery Systems ; Antineoplastic Agents/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Apoptosis/drug effects*

With the increasing utilization of cancer therapy, the incidence of lung injury associated with these treatments continues to rise. The recognition of pulmonary toxicity related to cancer therapy has become increasingly critical, for which interstitial lung disease (ILD) is a common cause of mortality. Cancer therapy-related ILD (CT-ILD) can result from a variety of treatments including chemotherapy, targeted therapy, immune checkpoint inhibitors, antibody-drug conjugates, and radiotherapy. CT-ILD may progress rapidly and even be life-threatening; therefore, prompt diagnosis and timely treatment are crucial for effective management. This review aims to provide valuable information on the risk factors associated with CT-ILD; elucidate its underlying mechanisms; discuss its clinical features, imaging, and histological manifestations; and emphasize the clinical-related views of its diagnosis. In addition, this review provides an overview of grading, typing, and staging treatment strategies used for the management of CT-ILD.
Humans ; Lung Diseases, Interstitial/diagnosis* ; Neoplasms/therapy* ; Risk Factors ; Immune Checkpoint Inhibitors/adverse effects* ; Antineoplastic Agents/therapeutic use*

This article provides an overview of the current evidence on the epidemiology, overlapping risk factors, and pathophysiology of cardiovascular disease (CVD) in patients with cancer. It explores the cardiotoxic effects of anticancer therapy and their impact on prognosis. Although cancer survival rates have improved over the last two decades, the risk of CVD has risen over time in patients with cancer. CVD and cancer share similar risk factors and a common pathophysiology involving inflammation. Many chemotherapeutic agents used to treat cancer are associated with cardiovascular complications (such as heart failure, myocardial infarction, and thrombosis). Current evidence indicates a significant burden of CVD in patients with cancer, particularly in the first year following cancer diagnosis, with elevated risk persisting beyond this period. This short- and long-term risk of CVD may vary depending on the cancer type and treatment regimen. Early identification of potential cardiovascular risk in patients with cancer, can lead to more favorable clinical and survival outcomes. Given the acute and long-term consequences, patients with cancer require increased cardiovascular care and lifestyle optimization. This article offers valuable insights into the cardiovascular burden and needs of patients with cancer. It is intended for a general medical research readership interested in the intersection of cardiology and oncology.
Humans ; Neoplasms/drug therapy* ; Cardiovascular Diseases/etiology* ; Prognosis ; Risk Factors ; Antineoplastic Agents/therapeutic use*

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have emerged as critical agents for cancer therapy. By inhibiting the catalytic activity of PARP enzymes and trapping them in the DNA, PARPis disrupt DNA repair, ultimately leading to cell death, particularly in cancer cells with homologous recombination repair deficiencies, such as those harboring BRCA mutations. This review delves into the mechanisms of action of PARPis in anticancer treatments, including the inhibition of DNA repair, synthetic lethality, and replication stress. Furthermore, the clinical applications of PARPis in various cancers and their adverse effects as well as their combinations with other therapies and the mechanisms underlying resistance are summarized. This review provides comprehensive insights into the role and mechanisms of PARP and PARPis in DNA repair, with a particular focus on the potential of PARPi-based therapies in precision medicine for cancer treatment.
Humans ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Neoplasms/genetics* ; DNA Repair/drug effects* ; Animals ; Antineoplastic Agents/therapeutic use*

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*