Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer / 中华消化外科杂志

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.

Lumican and tumor therapy resistance / 国际肿瘤学杂志

Lumican is a member of the small leucine-rich proteoglycan family, which is involved in cell processes related to tumorigenesis and development, such as epithelial-mesenchymal transition, cell proliferation, migration, invasion and adhesion. The expression of Lumican in different tumors is positively or negatively correlated with tumor progression, and can be used as a reference for tumor prognosis and efficacy evaluation. Further study of the correlation and potential mechanism between Lumican and tumor therapy resistance can provide new ideas for predicting clinical therapeutic efficacy.

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges / 医学前沿

Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

Research progress of circular RNA in drug resistance of liver cancer / 中国药理学通报

Circular RNAs are novel non-coding RNAs with multiple biological functions, which can participate in biological processes such as the occurrence, development, invasion, and metastasis of liver cancer, as well as drug resistance of liver cancer. This article reviews the roles and mechanisms of circR-NAs in chemotherapy resistance, targeted therapy resistance and immunotherapy resistance in liver cancer, in order to provide new ideas for solving liver cancer resistance.

Emerging roles of Aurora-A kinase in cancer therapy resistance

Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

Lineage plasticity-mediated therapy resistance in prostate cancer / 亚洲男科学杂志(英文版)

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Lineage plasticity-mediated therapy resistance in prostate cancer / 亚洲男科学杂志(英文版)

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Research progress on the role of epidermal growth factor receptor in human head and neck squamous cell carcinomas / 中国肿瘤临床

Head and neck squamous cell carcinoma(HNSCC)is a common malignant tumor with a relatively high degree of malignan-cy,which often induces recurrence and metastasis.Epidermal growth factor receptor(EGFR)is an important oncogene that is overex-pressed in HNSCC and is negatively correlated with prognosis,making it an important therapeutic target.However,EGFR-targeted ther-apy for HNSCC is not as effective as it is for non-small cell lung cancer.Recent studies have found that EGFR can promote resistance of tumor cells to therapeutic agents via its overexpression,mutation,single nucleotide polymorphism,nuclear translocation,and induc-tion of autophagy.This article will review these aspects and discuss how to utilize EGFR more effectively in treating HNSCC,and also provide a new direction for exploring therapeutic strategies for HNSCC.

Advance in resistance mechanism of cancer stem cells therapy / 药学实践杂志

Lung cancer is the leading cause of cancer deaths worldwide.Recurrence and metastasis are the primary reasons for its poor prognosis.Growing evidence has proposed that lung cancer may be driven by cancer stem cells (CSCs), which may be responsible for the poor outcome of lung cancer.The resistance mechanisms of cancer stem cells include four aspects: high expression of the chemo-resistant efflux transporter ABC in CSCs populations, over-expression of ALDH, efficient DNA damage repair system, developmental pathway activation.The tolerance mechanism of CSCs was described to provide theoretical basis for clinical treatment and development of new anti-tumor drugs.

Advances in the study of long non-coding RNA in the therapy resistance of breast cancer / 医学研究生学报

The occurrence of breast cancer therapy resistance is one of the most important reasons for the failure of breast cancer treatment.Once there was therapy resistance,breast cancer patients will suffer from advance of the cancer,replace of the tumor and distance metastasis,which will cause decrease of the quality of life and increase of the mortality rate.Long non-coding RNA (lncRNA) plays a very important role in the tumorigenesis and development.There are few reports about lncRNA in the resistance of breast cancer at home and abroad,especially in the field of molecular targeted therapy.However,understanding the role of lncRNA in the therapy resistance of breast cancer can effectively improve the effectiveness of several treat approaches of breast cancer.This article reviews the function of lncRNA in breast cancer chemotherapy,endocrine therapy and molecular targeted therapy and further clarify its molecular mechanism.

Resistance mechanisms underlying the EGFR-targeted therapies in glioblastoma / 国际药学研究杂志

Glioblastoma multiforme (GBM) is the most common primary malignant neoplasm of the central nervous system in adults. Previous work has shown that the over- expression of epidermal growth factor receptor (EGFR) and EGFR gene amplification was found in approximately 40- 60% of GBM patients, of which about 40% with EGFR mutations. Presently, multiple therapeutic drugs targeting EGFR have been used in clinical trials. However EGFR targeted therapy has limited efficacy in patients with GBM. It remains a haunting challenge to overcome the primary and secondary drug resistance to EGFR-targeted therapy in GBM patients. This review summarizes recent advances in the main resistance mechanisms underlying the EGFR-targeted therapies in glioblastoma.

Target for tumor hypoxia / 中国癌症杂志

Hypoxia, one major characteristic of malignant solid tumors, not only changes the biological characteristics of tumor cells, but also is the main cause of the failure for conventional chemotherapy and radiotherapy. This paper summarizes the implications of tumor hypoxia and the corresponding techniques,then we present the change in tumor biological characteristics induced by hypoxia. Next we analyze the cause of tumor resistance to chemotherapy and radiotherapy. And finally,We discuss the three antitumor strategies targeting hypoxia, which opens a new path to conquer cancer.[