Dataset Information

Update on Chemoresistance Mechanisms to First-Line Chemotherapy for Gallbladder Cancer and Potential Reversal Strategies.

ABSTRACT:

Objective

Gallbladder cancer (GBC) mortality remains high and chemoresistance is increasing. This review consolidates what is known about the mechanisms of chemoresistance to inform and accelerate the development of novel GBC-specific chemotherapies.

Methods

Studies related to GBC-related chemoresistance were systematically screened in PubMed using the advanced search function. Search terms included GBC, chemotherapy, and signaling pathway.

Results

Analysis of existing studies showed that GBC has poor sensitivity to cisplatin, gemcitabine (GEM), and 5-fluorouracil. DNA damage repair-related proteins, including CHK1, V-SCR, and H2AX, are involved in tumor adaptation to drugs. GBC-specific chemoresistance is often accompanied by changes in the apoptosis and autophagy-related molecules, BCL-2, CRT, and GBCDRlnc1. CD44 + and CD133 + GBC cells are less resistant to GEM, indicating that tumor stem cells are also involved in chemoresistance. In addition, glucose metabolism, fat synthesis, and glutathione metabolism can influence the development of drug resistance. Finally, chemosensitizers such as lovastatin, tamoxifen, chloroquine, and verapamil are able improve the therapeutic effect of cisplatin or GEM in GBC.

Conclusions

This review summarizes recent experimental and clinical studies of the molecular mechanisms of chemoresistance, including autophagy, DNA damage, tumor stem cells, mitochondrial function, and metabolism, in GBC. Information on potential chemosensitizers is also discussed. The proposed strategies to reverse chemoresistance should inform the clinical use of chemosensitizers and gene-based targeted therapy for this disease.

SUBMITTER: Lai J

PROVIDER: S-EPMC10030176 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Update on Chemoresistance Mechanisms to First-Line Chemotherapy for Gallbladder Cancer and Potential Reversal Strategies.

Lai Jinbao J Yang Songlin S Lin Zhuying Z Huang Wenwen W Li Xiao X Li Ruhong R Tan Jing J Wang Wenju W

American journal of clinical oncology 20230303 4

<h4>Objective</h4>Gallbladder cancer (GBC) mortality remains high and chemoresistance is increasing. This review consolidates what is known about the mechanisms of chemoresistance to inform and accelerate the development of novel GBC-specific chemotherapies.<h4>Methods</h4>Studies related to GBC-related chemoresistance were systematically screened in PubMed using the advanced search function. Search terms included GBC, chemotherapy, and signaling pathway.<h4>Results</h4>Analysis of existing stud ...[more]

PMID: 36867653

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Project description:BackgroundTo further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up.Patients and methodsAdult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs.ResultsWith a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation.ConclusionsWith a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Dataset Information

Update on Chemoresistance Mechanisms to First-Line Chemotherapy for Gallbladder Cancer and Potential Reversal Strategies.

Objective

Methods

Results

Conclusions

Publications

Update on Chemoresistance Mechanisms to First-Line Chemotherapy for Gallbladder Cancer and Potential Reversal Strategies.

Similar Datasets

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