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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Taxanes are essential chemotherapy agents for breast cancer treatment. However, patients frequently experience chemotherapy-induced peripheral neuropathy (CIPN) during their course of treatment. Cryotherapy is a non-pharmacological approach that has been explored for its potential effects on preventing or improving CIPN. However, although several studies have reported on the effects of cryotherapy, no comprehensive review has been conducted to confirm its benefits.

Checkpoint inhibitor pneumonitis (CIP) is a rare type of immune-related adverse reaction, that can seriously affect the subsequent anti-tumor immunotherapy and even lead to respiratory failure or death. However, if identified and diagnosed early, and treated promptly and appropriately, most patients have a good prognosis, and some may be eligible for subsequent immune rechallenge. In order to standardize diagnosis and treatment of patients with CIP and improve their prognosis, the Department of Pulmonary and Critical Care Medicine of Peking Union Medical College Hospital initiated and developed the consensus, which was discussed and reached a consensus by experts from the Oncology Respiratory Disease Committee of China Anti-Cancer Association, Lung Cancer Group of Thoracic Society of Chinese Medical Association and Beijing Cancer Prevention and Treatment Research Association. The consensus formed 18 expert recommendations on the risk factors, clinical characteristics, diagnostic evaluation measures, diagnostic criteria, differential diagnosis, treatment strategies and rehabilitation plans of CIP for clinicians' reference.

Objective: To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) . Methods: A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph(+) patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results: According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) (n=4), B/myeloid MPAL (n=7), and ALAL- not otherwise specified (n=2). Of the seven patients with B/myeloid MPAL, four were Ph(+) and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion: Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

Lung cancer is the leading cause of cancer-related deaths worldwide, characterized by high incidence and mortality rates. The primary reasons for treatment failure in lung cancer patients are tumor invasion and drug resistance, particularly resistance to chemotherapeutic agents and epidermal growth factor receptor (EGFR) mutant targeted therapy, which considerably undermine the therapeutic outcomes for those with advanced lung cancer. Epithelial-mesenchymal transition (EMT) serves as a crucial biological process closely associated with physiological or pathological processes such as tissue embryogenesis, organogenesis, wound repair, and tumor invasion. Numerous studies have indicated that EMT, mediated through various signaling pathways, plays a pivotal role in the initiation, progression, and metastasis of lung cancer, while it is also closely associated with drug resistance in lung cancer cells. Therefore, research focusing on the molecular mechanisms and pathophysiology related to EMT can contribute to reversing drug resistance in drug treatment for lung cancer, thereby improving prognosis. This article reviews the progress in research on EMT in the invasion, metastasis, and drug resistance of lung cancer based on relevant domestic and international literature.

To observe the effects of moxibustion combined with chemotherapy on immune checkpoints including programmed cell death protein 1 (PD-1), T cell immunoglobulin domain and mucin domain (TIM-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in the tumor tissue of breast cancer-bearing mice, so as to explore the effect and mechanisms of moxibustion combined with chemotherapy on breast cancer.

Myelosuppression is a common hematological side effect of oncological treatment, mainly including neutropenia, thrombocytopenia and anemia. Due to the delay in its clinical manifestation, a well-established out-of-hospital management system can help clinicians better prevent and manage the myelosuppression associated with oncology treatment and ensure the effectiveness and safety of antitumor therapy. This consensus focuses on a detailed compilation and summary of the definition and grading of myelosuppression associated with oncological treatment, the principles of out-of-hospital management, the management process and management methods, develops a risk stratification assessment table for oncology treatment-related myelosuppression, and puts forward 8 recommendations based on the risk stratification, which is aimed at providing medical workers with a reference plan for the out-of-hospital management of myelosuppression associated with oncological treatment.

Immune checkpoint inhibitor (ICI) has been widely used in lung cancer patients. While ICI treatment improves the overall survival of patients, it can also lead to a series of immune-related adverse events (irAE). Severe irAE should be treated with glucocorticoids and biological agents. Opportunistic infections should be highly vigilant during the treatment of glucocorticoids and biological agents. We report a patient with locally advanced non-small cell lung cancer who developed severe ICI-related colitis after chemotherapy combined with immunotherapy. The patient developed hematogenous disseminated Mycobacterium tuberculosis infection and pulmonary aspergillosis during the treatment with glucocorticoids and biological agents (infliximab). The purpose of this study is to draw the attention of clinicians to opportunistic infections when dealing with irAE.

In the real world, the plasma drug concentration range of Icotinib treated with epidermal growth factor receptor (EGFR) gene mutant non-small cell lung cancer (NSCLC) is not yet clear, and there may be a correlation between drug concentration and its efficacy, as well as adverse reactions. This study conducted therapeutic drug monitoring (TDM) of Icotinib. The aim of this study was to analyze the drug exposure of Icotinib in targeted therapy for NSCLC, and to investigate the relationship between Icotinib drug concentration and its efficacy and safety.

Chemotherapy-induced anemia (CIA) is one of the most common complications in cancer patients. If CIA treatment is not effective, it will affect the normal implementation of chemotherapy regimens, and reduce the quality of life of patients and shorten clinical survival. At present, CIA has serious shortcomings in treatment rate and unsatisfactory therapeutic effect. It is often forced to reduce the dose of chemotherapy or delay chemotherapy due to anemia that cannot be rapidly and effectively treated in clinical practice. These problems are mainly related to factors such as complex etiology of the disease, late timing of clinical intervention, and certain limitations in existing treatment options. Therefore, disease management needs to further strengthen the concept of early diagnosis and early treatment to avoid the increased clinical burden due to the severity of anemia. Meanwhile, with the in-depth understanding of the mechanism of anemia, new drug research and development based on the comprehensive regulatory mechanism of hypoxia-inducible factor (HIF) has begun in clinical practice. A phase Ⅲ clinical study of Roxostat in the treatment of chemotherapy-induced anemia in patients with non-medullary malignancies was presented at the European Society of Medical Oncology (ESMO) conference in 2023. This hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) drug is an oral preparation, which has shown good efficacy and safety in the study, and has superior compliance compared with recombinant human erythropoietin-α (rHuEPO-α). Starting from the re-understanding of the mechanism of CIA, this review analyzes the current diagnosis and treatment dilemmas of CIA, puts forward suggestions in combination with the "Guildlines of Chinese Society of Clinical Oncology (CSCO) clinical practice in tumor-related anemia (2024)", and introduces and looks forward to HIF-PHI, a new therapeutic drug in the future.

Based on the epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase(MAPK) signaling pathway-mediated cell proliferation, this study explores the effect of cisplatin combined with Guiqi Yiyuan Ointment on Lewis lung cancer-bearing mice. A total of 60 male C57BL/6 mice were randomly divided into a blank group with 10 mice and a modeling group with 50 mice. After modeling, they were randomly divided into the model group, cisplatin group, and low-, medium-, and high-dose groups of cisplatin combined with Guiqi Yiyuan Ointment, with 10 mice in each group. After 14 days of medication, the general condition of the mice was observed; body weight was measured, and organ index and tumor inhibition rate were calculated. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology changes in tumor tissue. Immunohistochemistry was used to detect the positive rate of Ki-67 antigen(Ki-67) and proliferating cell nuclear antigen(PCNA) in tumor tissue. Western blot and real time-quantitative polymerase chain reaction(qPCR) were used to detect the expression of related proteins and mRNA in tumor tissue. Flow cytometry was used to detect the cell cycle of tumor cells in tumor tissue. The results showed that compared with that in the blank group, the general condition of mice in the model group deteriorated; the body weight, as well as thymus and spleen index of mice in the model group decreased after 14 days of medication. Compared with that in the model group, the general condition of mice in the cisplatin group deteriorated, while the condition of mice in the combined groups improved; the body weight, as well as thymus and spleen index of mice in the cisplatin group decreased, while the three indicators in the combined groups increased; the tumor weight of each medication group decreased, and the tumor inhibition rate increased; there were varying degrees of necrosis in tumor cells of each medication group, and the tightness of tumor cells, the increase in the number of cell nuclei and chromatin, and mitosis all decreased. The positive rate of Ki-67 and PCNA, as well as the protein expression and ratio of p-EGFR/EGFR, rat sarcoma viral oncogene homolog(Ras), phosphorylated Raf-1 protein kinase(p-Raf-1)/Raf-1, phosphorylated mitogen-activated protein kinase kinase(p-MEK)/MEK, phosphorylated extracellular signal-regulated kinase(p-ERK)/ERK and the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK all decreased. The proportion of tumor cells in the G_0/G_1 phase of each medication group increased, and that in the S phase decreased. In addition, there was no significant difference in the G_2/M phase. Compared with that of the cisplatin group, the tumor weight of the combined groups decreased, and the tumor inhibition rate increased. The necrosis and mitosis of tumor cells in the combined groups were more pronounced; the positive rate of Ki-67 and PCNA, the protein expression and ratio of p-EGFR/EGFR, Ras, p-Raf-1/Raf-1, p-MEK/MEK, and p-ERK/ERK, as well as the mRNA expression of EGFR, Ras, Raf-1, MEK, and ERK in the combined groups all decreased. The proportion of tumor cells in the G_0/G_1 phase of the combined medium-and high-dose groups increased, and that in the S phase decreased. There was no significant difference in the proportion of tumor cells of the combined groups in the G_2/M phase. This indicates that the combination of cisplatin and Guiqi Yiyuan Ointment can enhance the anti-tumor effect of cisplatin on tumor-bearing mice, and the mechanism may be associated with the inhibition of the EGFR/MAPK pathway, which accelerates the arrest of tumor cells in the G_0/G_1 phase, thereby inhibiting the proliferation of tumor cells. At the same time, the study also indicates that Guiqi Yiyuan Ointment may reduce the damage of tumors to mice and the toxic side effects brought by cisplatin chemotherapy.

Stevens-Johnson syndrome (SJS) and toxic epidermalnecrolysis (TEN) are acute, severe and fatal diseases involving the skin and mucous membranes, most commonly caused by pharmaceutical factors. These include various sensitizing antibiotics, non-steroidal anti-inflammatory drugs and so on. Immune-associated Stevens-Johnson syndrome/toxic epidermolysis caused by programmed death-1 (PD-1) inhibitors has not been reported. On April 11, 2024, a male patient with primary bronchial lung cancer (right lung squamous cell carcinoma T3N3M1b ⅣA phase driver gene KRAS G12S PD-L1 negative, PS 0 score) was admitted to the department of respiratory and critical care medicine of Bishan hospital affiliated to Chongqing medical university. On March 25, 2024, the patient underwent the 3rd cycle of anti-tumor therapy "Tirellizumab 200 mg+albumin paclitaxel 400 mg+carboplatin 450 mg", and on April 9, 2024, Stevens-Johnson syndrome and toxic epidermolysis occurred, and the epidermolysis area reached more than 95%. After permanent discontinuation of immunosuppressants, anti-infection, hormone, nutritional support, immunoglobulin and other comprehensive treatment, the patient was eventually cured and successfully discharged.

Lung cancer is one of the most malignant tumor, representing a significant threat to human health. In China, its mortality rate is the highest among all malignant tumors. The occurrence of drug resistance has resulted in unfavourable prognosis for patients with lung cancer, and overcoming drug resistance is a significant challenge that needs to be addressed. Nano-drug delivery technology has been an important approach to overcome drug resistance in lung cancer. Targeting to the mechanisms of drug resistance, by enabling the combined delivery of drugs, increasing the efficiency of drug delivery and improving the targeting and safety of drugs, nano-drug delivery technology offers a novel approach to tackling drug resistance in lung cancer. This paper describes the current status of lung cancer treatment, mechanisms of drug resistance, strategies to overcome drug resistance, and the application of nanotechnology in the diagnosis and treatment of lung cancer. In addition, it summarizes the recent research progress on the application of nano-drug delivery technology to overcome drug resistance in lung cancer. Finally, the current prospects and challenges of nano-drug delivery technology are discussed.
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Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations.

Objective To study the impacts of curcumin on the proliferation, migration and cisplatin (DDP) resistance of bladder cancer cells by regulating the liver kinase B1-AMP activated protein kinase-microtubule-associated protein 1 light chain 3 (LKB1-AMPK-LC3) signaling pathway. Methods Human bladder cancer cell line T24 was cultured in vitro, and its DDP resistant T24/DDP cells were induced by cisplatin (DDP). After treating T24 and T24/DDP cells with different concentrations of curcumin, the optimal concentration of curcumin was screened by MTT assay. T24 cells were randomly grouped into control group, curcumin group, metformin group, and combination group of curcumin and metformin. After treatment with curcumin and LKB1-AMPK activator metformin, the proliferation, autophagy, migration, and apoptosis of T24 cells in each group were detected by MTT assay, monodansylcadavrine (MDC) fluorescence staining, cell scratch assay, and flow cytometry, respectively. Western blot was used to detect the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24 cells of each group. T24/DDP cells were randomly assigned into control group, curcumin group, metformin group, and combination group of curcumin and metformin. Cells were treated with curcumin and metformin according to grouping and treated with different concentrations of DDP simultaneously. Then, the effect of curcumin on the DDP resistance coefficient of T24/DDP cells was detected by MTT assay. T24/DDP cells were randomly grouped into control group, DDP group, combination groups of DDP and curcumin, DDP and metformin, DDP, curcumin and metformi. After treatment with DDP, curcumin, and metformin, the proliferation, autophagy, migration, apoptosis, drug resistance, and the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24/DDP cells of each group were detected with the same methods. Results Compared with the control group, the activity of T24 cells, relative number of autophagosomes, migration rate, Phosphorylated-LKB1 (p-LKB1)/LKB1, Phosphorylated-AMPK (p-AMPK)/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the curcumin group were lower, and the apoptosis rate of T24 cells was higher; the changes in various indicators in the metformin group were opposite to those in the curcumin group. Compared with the curcumin group, the activity of T24 cells, relative number of autophagosomes, migration rate, p-LKB1/LKB1, p-AMPK/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the combination group of curcumin and metformin were higher, and the apoptosis rate of T24 cells was lower. Compared with the control group, there were no obvious changes in various indicators of T24/DDP cells in the DDP group. Compared with the control group and DDP group, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-glycoprotein (P-gp) protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP and curcumin were lower, and the apoptosis rate of T24/DDP cells was higher; the changes in the above indicators in the combination group of DDP and metformin were opposite to those in the combination group of DDP and curcumin. Compared with the combination group of DDP and curcumin, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-gp protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP, curcumin and metformin were higher, and the apoptosis rate of T24/DDP cells was lower. Conclusion Curcumin can reduce the activity of LKB1-AMPK-LC3 signaling pathway, thereby inhibiting autophagy, proliferation and migration of bladder cancer cells, promoting their apoptosis, and weakening their resistance to DDP.

With the widespread application of systemic treatments for hepatocellular carcinoma, liver injury caused by molecular targeted drugs and immune checkpoint inhibitors has become a common clinical problem. The Chinese Society of Hepatology organized relevant domestic experts to summarize and analyze the adverse liver reactions and diagnosis and treatment progress related to systemic treatment of liver cancer at home and abroad, and formulated the "Consensus on the management of liver injury associated with targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma," aiming to provide reasonable suggestions and decision-making references for clinical physicians in liver disease and related specialties in the monitoring, diagnosis, prevention and treatment of liver injury during the treatment of targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma, so as to enable more liver cancer patients to benefit from targeted immune therapy.

Immune checkpoint inhibitors (ICPis) significantly improves survival in a number of cancer patients by blocking immunosuppressive molecules and reactivating the function of effector T cells to specifically kil tumor cells. This article reports a case of secondary hypoadrenocorticism caused by programmed death 1 (PD-1) inhibitor related hypophysitis. A 65-year-old male patient received immunotherapy for right lung squamous cell carcinoma invading the chest wall (cT4N2M0) for 4 times. Two weeks after the last immunotherapy treatment, the patient experienced poor appetite and fatigue. Examination results indicated severe hyponatremia, and there was no improvement even after repeated supplementation with high-concentration sodium chloride. After further examination, glucocorticoid supplementation was given to the patient and his clinical symptoms were significantly improved. It is recommended that patients receiving ICPis should be asked in detail about their medical history before initiating treatment, baseline screening should be carried out reasonably, and regular follow-up about endocrine gland hormone and related biochemical indexes after treatment should be carried out. Meanwhile, it is necessary to pay attention to the related symptoms and signs of patients in order to find endocrine gland adverse reactions in time.