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Introduction: Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched., Methods: In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance., Results: Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed PRICKLE3 , TNFSFI0 , ACSLl and EP300 as potential contributors to primary resistance, with SNWl , SENP2 and SMNDCl emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC., Discussion: These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Fan, Yang and Cun.)

Immunotherapy treatments, particularly immune checkpoint blockade, can result in benefits in clinical settings. But many pre-clinical and clinical studies have shown that resistance to anti-PD1 therapy frequently occurs, leading to tumor recurrence and treatment failure, including in patients with hepatocellular carcinoma (HCC). In this study, 10 patients with HCC were remedied with anti-PD1, and pre-treatment biopsy samples were sequenced for 289 nanostring panel RNA to compare responsive and non-responsive tumors to identify possible pretreatment biomarkers or targets of anti-PD1 therapeutic responses. Fortunately, the expression of β-Glucuronidase (GUSB) in the non-responding tumors was found to be remarkably higher than that in responding tumors. Results of the cell counting kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell, wound healing test, and flow cytometry showed that GUSB facilitated proliferation, invasion, as well as migration of human HCC cells and downregulated PD-L1 expression by promoting miR-513a-5p. Additionally, as a GUSB inhibitor, amoxapine can reduce the progression of human HCC cells, and was an effective treatment for HCC and improved the sensitivity of anti-PD1 therapy. In summary, this study reveals that increased GUSB downregulates PD-L1 expression by promoting miR-513a-5p, leading to primary resistance to anti-PD1 treatment in HCC, and amoxapine enhances the sensitivity of anti-PD1 therapy by inhibiting GUSB, providing a new strategy and method for improving the efficacy of anti-PD1 therapy and bringing new prospects for therapy of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kong, Zheng, Song, Zhang, Liu, Kang, Sun, Sun, Huang, Li, Rong, Wang, Tang and Xia.)

Background: Immunotherapy has become the standard of care for non-small cell lung cancer (NSCLC) patients. Some patients experience primary resistance to immunotherapy. Currently, we lack a marker of resistance to immunotherapy. Myeloid-derived suppressive-like cells (MDSCs) can reduce tumor response rate and survival outcomes., Methods: This is an exploratory prospective observational study on metastatic NSCLC patients starting immunotherapy. Baseline peripheral blood samples were collected. Monocytic (M)-MDSCs were analyzed by flow cytometry. The main clinical outcomes were tumor response, progression-free survival (PFS), and overall survival (OS). The association between MDSC levels and tumor response was assessed. The association of PFS with OS was investigated using the Kaplan-Meier method and the Cox proportional hazards model., Results: Twenty-two patients were included. The median M-MDSC value was higher in patients with progressive disease than patients with stable disease or partial response, p = 0.045. The median MDSC value in the overall population was 1.9. We found worse PFS (HR = 2.51; p = 0.046) and OS (HR = 2.68; p = 0.042) in patients with M-MDSC values higher than the median., Conclusions: In this exploratory analysis, high M-MDSC levels are strongly associated with primary resistance to immunotherapy. If validated in larger studies, MDSC levels in blood samples could help to select NSCLC patients for higher benefit from immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bronte, Petracci, De Matteis, Canale, Zampiva, Priano, Cravero, Andrikou, Burgio, Ulivi, Delmonte and Crinò.)

Lung cancer is the leading cause of cancer-related deaths worldwide. As the most prevalent molecular mutation subtypes in non-small cell lung cancer (NSCLC), EGFR-TKIs are currently a standard first-line therapy for targeting the mutated EGFR in advanced NSCLC patients. However, 20-30% of this subset of patients shows primary resistance to EGFR-TKIs. Patients with co-mutations of EGFR and several other genes have a poor response to EGFR-TKIs, whereas the prognostic and predictive significance of EGFR/TP53 co-mutation in NSCLC patients remains controversial. Meanwhile, little is known about how to choose an optimal therapeutic strategy for this subset of patients. Presently, no drugs targeting TP53 mutations are available on the market, and some p53 protein activators are in the early stage of clinical trials. A combination of EGFR-TKIs with antiangiogenic agents or chemotherapy or other agents might be a more appropriate strategy to tackle the problem. In this review, we describe the prognostic and predictive value of EGFR/TP53 co-mutation in NSCLC patients, investigate the mechanisms of this co-mutation affecting the response to EGFR-TKIs, and further explore optimal regimens effectively to prolong the survival time of the NSCLC patients harboring this co-mutation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yu, Zhang and Liu.)

In this study, we evaluated clinical parameters to predict the primary resistance of palbociclib in combination with endocrine therapy as the first-line treatment in patients with hormone receptor (HR)+, human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer (MBC). We performed a data analysis of patients diagnosed with HR+, HER2-MBC who received palbociclib plus letrozole as the first-line treatment in the metastatic setting from the clinical data warehouse in Samsung Medical Center. In this study, 305 patients were included in the final data analysis. The median follow-up duration was 31 months, and we observed 123 cases of disease progression. The median progression-free survival (PFS) was 28.7 months, and 38 patients (12.5%) had less than a 6-month PFS. The multivariate analysis suggested that primary resistance to adjuvant endocrine therapy (ET) (hazard ratio: 1.91), presence of liver metastasis (hazard ratio: 2.17), initial elevation of serum CA-15-3 (hazard ratio: 1.99), weak positivity of estrogen receptor (ER) (hazard ratio: 2.28), Ki-67 3+ or 4+ (hazard ratios: 2.58 and 10.28), and presence of mutation (hazard ratio: 9.59) were associated with a short PFS duration. A further prediction model was developed with data from 256 patients and 33 cases of disease progression in 6 months. This model included five factors-primary resistance to adjuvant ET (odds ratio, OR: 1.14), liver metastasis (OR: 1.56), initial CA-15-3 elevation (OR: 1.51), weak ER expression (OR: 2.22), and BRCA2 mutation (OR: 2.85)-and the area under the receiver operating characteristic curve was 0.842 (95% CI: 0.775, 0.909; p < 0.001). Finally, we divided them into four risk groups according to the prediction model with the five risk factors. These four groups had different PFS ( p < 0.001) and primary resistance of palbociclib with letrozole [OR of group 2 vs. group 1 (ref): 2.18 ( p = 0.002), OR of group 3: 3.91 ( p < 0.001), and OR of group 4: 4.25 ( p < 0.001)]. We developed a prediction model of primary resistance to palbociclib with letrozole as the first-line treatment for HR+, HER2-MBC. Our prediction model might be helpful for considering the first-line treatment strategies. Further well-designed clinical trials would be warranted to validate our prediction model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Oh, Park, Ahn and Im.)

Background: CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10-20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem., Case Description: A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020., Conclusion: CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, Zhao, Wang, Wang, Qin, Zhu, Wu, Liu, Zheng, Zheng and Chen.)

Our ability to detect and directly target the oncogenic alterations responsible for tumor proliferation has contributed significantly to the management of lung cancer in the last decade. The therapeutic efficacy of molecularly targeted therapy is, however, mainly limited to patients harboring certain genetic mutations and is generally short-lived. Herein, we review primary and secondary drug resistance using the most well-studied of the molecularly targeted agents, the tyrosine kinase inhibitors targeting the epidermal growth factor (EGF) receptor, and the anaplastic lymphoma kinase (ALK) rearrangement, the current limitations of targeted therapies and their consequences on the management of patients with lung cancer.