Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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In recent years, antibody-drug conjugates (ADCs) have achieved remarkable progress in the treatment of solid tumors and are now widely applied in malignancies such as breast cancer, ovarian cancer, cervical cancer, urothelial carcinoma, and non-small cell lung cancer, demonstrating favorable clinical efficacy. However, with their expanding clinical use, safety challenges associated with ADCs have become increasingly apparent. Among these, ocular adverse events have received limited attention in the past but is now emerging as a clinically relevant concern, as it may impair patients' quality of life and necessitate treatment modifications. Due to differences in payloads, target specificity, and mechanisms of action, various ADCs may induce ocular adverse events, including corneal disorders such as dry eye and keratoconjunctivitis, which can lead to visual disturbances, diminished quality of life, and reduced treatment adherence. Consequently, appropriate preventive and management strategies are urgently needed in clinical practice. To address this gap, and based on the latest international and domestic clinical evidence as well as multidisciplinary expert experience in oncology and ophthalmology, a Chinese expert consensus was developed following extensive discussion. This consensus aims to enhance clinicians' awareness of ADC-associated ocular adverse events, promote the safe application of ADCs in the treatment of solid tumors, and ultimately improve patients' quality of life and therapeutic outcomes.

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) is a crucial signaling network regulating cell proliferation, survival, and metabolism, which plays a central role in the pathogenesis and progression of breast cancer. Targeting the PAM pathway with inhibitors provides a novel precision therapeutic option for cancer patients. However, the broad suppression of physiological PAM pathway functions in normal tissues, combined with the distinct characteristics of their molecular targets, leads to both the uniqueness of adverse reactions associated with these agents and heterogeneity within their safety profiles. Given the complexity of the adverse reaction spectrum and the specialized management requirements for PAM pathway inhibitors, Cancer Drug Clinical Research Committee of China Anti-Cancer Association and Standard Construction Committee of China Anti-Cancer Association jointly convened a multidisciplinary expert panel to develop this consensus. This document systematically synthesizes epidemiological features, pathological mechanisms, and risk factors of PAM pathway inhibitor-associated adverse reactions. It provides clinicians with evidence-based guidance on standardized prevention strategies, early warning systems, assessment frameworks, intervention protocols, and long-term monitoring pathways. The ultimate goals are to maximize medication safety, optimize treatment adherence, and ultimately enhance antitumor efficacy and patient quality of life.

With the expanding use of immune checkpoint inhibitors (ICIs) in gastric cancer, surgical safety is facing new challenges. Perioperative immune-related adverse events (irAEs) can substantially overlap with postoperative complications in both time course and clinical presentation, increasing the risk of diagnostic confusion, missed or delayed recognition, and potentially fatal outcomes. Integrating evidence from prior studies and real-world clinical experience, this article focuses on perioperative irAEs in gastric cancer that are particularly prone to misclassification, such as ICI-related pneumonitis, hypophysitis, adrenal insufficiency, and hypothyroidism. We systematically summarize their epidemiology and common manifestations and, using a symptom-oriented approach, address typical perioperative scenarios including fatigue, hypotension, electrolyte disturbances, altered mental status, postoperative fever, hypoxemia, dyspnea, cough, and perioperative enzyme abnormalities. Practical diagnostic clues and management strategies are proposed to distinguish irAEs from surgical complications such as infection, hemorrhage, pulmonary complications, myocardial infarction, and surgery-related pancreatic injury. We further emphasize the need to establish a standardized, multidisciplinary team-based perioperative pathway in the era of neoadjuvant immunotherapy, incorporating comprehensive preoperative baseline assessment of cardiac, pulmonary, hepatic, and endocrine function; protocolized postoperative monitoring at key time points; and risk-stratified interventions. When irAEs are suspected, early specialist consultation and timely initiation of immunosuppressive therapy, particularly corticosteroids, are critical to reducing both diagnostic delay and unnecessary overtreatment, thereby maximizing the therapeutic benefit of immunotherapy while safeguarding surgical outcomes.

In recent years, immune checkpoint inhibitors (ICIs), as a revolutionary therapeutic approach in oncology, have demonstrated remarkable clinical efficacy across various malignant tumors. With the widespread clinical application of ICIs, their associated toxicities have emerged as a critical issue that urgently requires resolution in the field of cancer immunotherapy. ICIs-associated pneumonitis (CIP) specifically refers to immune-related adverse events (irAEs) of the lung induced by ICIs therapy, the underlying pathogenesis of which remains incompletely elucidated. As a rare yet severe complication of ICIs treatment, and CIP is characterized by insidious onset, rapid progression, poor prognosis, and high mortality rate, with highly heterogeneous clinical manifestations and radiological features. Due to the lack of specific biomarkers and objective diagnostic indicators, the early identification and diagnosis of CIP present significant clinical challenges. By reviewing previous literature and studies, this paper summarizes recent advances in understanding the clinical manifestations, risk factors, potential molecular mechanisms, biomarkers, and early warning systems of CIP in patients receiving immunotherapy for lung cancer. The aim of this article is to provide a reference for the clinical management of CIP and offer a theoretical basis for establishing an early screening and precision diagnosis and treatment system for this condition.
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Gastrointestinal malignant tumors are a group of severely life-threatening tumors. Their incidence and mortality rates consistently rank among the top 10 cancers worldwide and are increasing year by year. Based on his long-term clinical practice, Professor Zhou Zhongying proposes the theory of "cancer toxin". The research team led by Professor CHENG Hai-bo further establishes the pathogenesis theory of cancer toxin, holding that cancer toxin is the key factor in the occurrence and development of tumors, and thus taking "anti-cancer and detoxification" as the basic therapeutic principle. With the vigorous promotion of TCM, various active ingredients of TCM are extracted and make a difference in tumor therapy. These active ingredients can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an active ingredient extracted from the skin of Bufo gargarizans with detoxifying, anti-swelling, and pain-relieving effects and is widely used in the treatment of intermediate and advanced tumors. Clinical studies have revealed that cinobufotalin enhances tumor control rates, prolongs survival time, improves quality of life, and reduces the incidence of adverse reactions when combined with chemotherapy, radiotherapy, or targeted therapies. The mechanism studies have demonstrated that cinobufotalin plays a therapeutic role by inhibiting cell proliferation and invasion, inducing tumor cell apoptosis, modulating immune response, reversing drug resistance, etc. This paper reviews the research progress on cinobufotalin from the perspective of pathogenesis theory of cancer toxin through summarizing domestic and international reported research on clinical application and mechanism of cinobufotalin against gastrointestinal malignant tumors in recent years. The findings aim to provide a theoretical basis for research on the anti-tumor effect of cinobufotalin and a reference for standardized use and in-depth research of drugs.

In recent years, immune checkpoint inhibitor (ICI) therapy has achieved a breakthrough in cancer treatment. By targeting and blocking immune checkpoint molecules on T cells, ICIs release inhibited anti-tumor immune responses, demonstrating durable clinical efficacy and improved long-term survival across multiple cancer types. However, only a minority of cancer patients currently benefit from ICI treatment, with primary resistance observed in most malignancies. Clarifying the mechanisms underlying primary resistance to ICI therapy is conducive to the development of effective combination strategies for overcoming drug resistance. This review systematically examines the molecular basis of primary resistance to ICIs through following aspects: tumor lymphocyte infiltration phenotype, interferon signaling pathways, antigen presentation machinery, and tumor cell-intrinsic oncogenic signaling pathways, which may provide novel therapeutic targets and rational combination strategies for cancer immunotherapy.

The ubiquitin-proteasome system (UPS) serves as the central mechanism for protein degradation in eukaryotic cells. Deubiquitinases (DUBs), which maintain protein stability and function by removing ubiquitin chains play a key role in protein cycling. Consequently, a DUB-targeting chimera (DUBTAC) technology has emerged. A DUBTAC consists of three components: a protein-targeting ligand, a DUB recruiter, and a linker connecting them. A DUBTAC can simultaneously bind to its targeted protein and DUB and induce the DUB to cleave the ubiquitin chains, thereby restoring the protein function by stabilizing the target protein. The DUBTAC technology provides a novel research strategy involving targeted protein stabilization for conventionally "undruggable" proteins that are abnormally degraded. Compared with other mature technologies, such as proteolysis-targeting chimera (PROTAC) and molecular glue degrader technologies, the DUBTAC technology has the unique advantages of targeting and stabilizing tumor suppressors, thus showing high potential for cancer therapy. However, it is still in the early stage of development with few systematic summaries of recent research achievements. This review introduces the basic concepts, critical design, and research considerations of DUBTACs, summarizes the latest research advances in DUBTAC technology for antitumor drug development, and discusses the development strategies and clinical application prospects of DUBTACs in the future, aiming to provide more directions for research on this technology.

Immune checkpoint blockade (ICB) therapy has demonstrated significant efficacy in the treatment of various cancers. However, a subset of patients develops hyper-progressive disease (HPD) following ICB, which is characterized by accelerated tumor growth and poor clinical outcomes. This review outlines the clinical features, potential mechanisms, and possible intervention strategies of HPD, with the aim of informing clinical practice and providing relevant recommendations.
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Stathmin 1 (STMN1) is a microtubule-binding cytoplasmic phosphoprotein that promotes microtubule depolymerization or inhibits microtubule assembly, thereby regulating cytoskeletal organization and cell cycle progression. STMN1 is upregulated in a variety of malignant tumors, where it drives proliferation, invasion, metastasis, and angiogenesis through classic pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and ferroptosis. STMN1 can also modulate the function of immune cells, thereby influencing antitumor immunity. Clinical data show that its high expression correlates positively with tumor drug resistance and poor prognosis, suggesting that STMN1 has potential as a tumor biomarker and therapeutic molecular target with important clinical significance.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

Doxorubicin is a commonly used antitumor drug for the treatment of various cancers. However, its clinical application is greatly restricted by its severe cardiotoxicity. At present, doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms, depending on the dosage and duration of exposure, which may eventually lead to the occurrence of heart failure. The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress, mitochondrial damage, calcium overload, dysregulation of autophagy, and apoptosis. In forensic medical practice, cases of poisoning or even cardiac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations. The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years, analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin, and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Lung cancer is the cancer with the highest incidence and mortality rate worldwide. In addition to the diversified treatment and prolonged lifespan in view of the development of medical technology, the side effect of medicine should not be ignored. Drug-induced interstitial lung disease (DI-ILD) is also commonly encountered during this process, and ILD triggered by the treatment of lung cancer characterized by the inflammation and scarring of lung tissue after the antitumor treatment in lung cancer leads to a poor prognosis and high mortality. The diagnosis and treatment of ILD caused by anti-lung cancer agents remains challenging in clinical settings and requires joint efforts from multidisciplinary team (MDT). This review systematically updates the epidemiology, molecular pathogenesis, genomics/genetics study, diagnosis and treatment of ILD related to anti-lung cancer agents. By the integration of the latest evidences, the paper offers clinical work references for early diagnosis of ILD related to anti-lung cancer agents to enhance the survival and quality of life of the lung cancer patients.
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The application of small molecule targeted drugs for lung cancer has significantly improved the survival of lung cancer patients. However, these drugs have a wide variety of types, fast development and market launch of new drugs, complex adverse reactions, and are mostly used at home, which increases the risk of irrational drug use. At the same time, insufficient monitoring of efficacy and safety is also prone to occur, ultimately affecting treatment outcomes. This consensus focuses on 43 small molecule targeted drugs or combinations for lung cancer, providing standardized recommendations for rational drug use and monitoring of efficacy/adverse reactions in clinical practice. The recommendations are regarding drug selection, dosage adjustment, efficacy monitoring, adverse reaction monitoring, and improvement of patient compliance. This consensus aims to improve the rational use and efficacy/safety monitoring quality of small molecule targeted drugs for lung cancer, ensure the effectiveness and safety of drug treatment, prolong the survival of lung cancer patients and improve their quality of life.
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Antineoplastic drugs have clear health hazards to the human body. In recent years, the scale of use of antineoplastic drugs had continued to expand, and the occupational exposure risk of medical personnel had also increased, which had attracted widespread attention. Taking effective measures to prevent occupational exposure can protect the health of medical personnel. This article reviewed the laws, regulations, guidelines, and industry guidance documents on occupational exposure prevention and control of antineoplastic drugs issued by relevant departments and associations in China. It summarized the scientific management experience of antineoplastic drugs in China, with the aim of reducing the occupational exposure risk of antineoplastic drugs in the future, and assisting the healthy development of China's medical and health industry.

Moxibustion therapy is an important traditional non-pharmacological treatment in traditional medicine for improving chemotherapy-induced bone marrow suppression. By reviewing recent studies on moxibustion intervention for chemotherapy-induced bone marrow suppression, this article summarized and analyzed the current research status. In clinical studies, moxibustion therapy that tonifies the spleen, nourishes the kidneys, warms yang, and nourishes blood has been verified to be effective for chemotherapy-induced bone marrow suppression, but the efficacy may vary among individuals receiving different chemotherapy regimens. Experimental studies have shown that moxibustion therapy primarily improves chemotherapy-induced bone marrow suppression by repairing bone marrow tissue structure, increasing the amounts of hematopoietic stem cells, improving bone marrow hematopoietic microenvironment, repairing bone marrow cell DNA, and regulating signaling pathways such as Notch, Wnt, phosphatidylinositol 3-kinase/protein kinase B/ mammalian target protein of rapamycin and other signaling pathways. Future research can further systematically reveal the mechanisms of moxibustion therapy, such as alleviating hematopoietic stem cell aging induced by chemotherapy, regulating miRNAs to improve bone marrow suppression, and investigate the sensitivity of patients with bone marrow suppression caused by different chemotherapy regimens to moxibustion therapy, in order to complete and standardize the application protocols of moxibustion.

Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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