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

Lai, Jinbao; Yang, Shi Yu; Lin, Zhuying; Huang, Wenwen; Li, Xiao; Li, Ruhong; Jinquan, Tan; Wang, Wenju

doi:10.1097/coc.0000000000000989

Cited by 7 publications

(6 citation statements)

References 99 publications

(239 reference statements)

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“… 95 Interestingly, in general, the stemness of cancer cells is positively correlated with drug resistance, but the opposite effect is shown in GBC. 96 All the studies indicate that the characteristics of CD44 in GBC provide some new thought in diagnosis and treatment of GBC.…”

Section: Cd44 In Neoplastic Diseasesmentioning

confidence: 99%

CD44 and its implication in neoplastic diseases

Xu,

Bai,

Lan

et al. 2024

MedComm

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CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of CD44 gene, CD44 is divided into two isoforms, the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v). Different isoforms of CD44 participate in regulating various signaling pathways, modulating cancer proliferation, invasion, metastasis, and drug resistance, with its aberrant expression and dysregulation contributing to tumor initiation and progression. However, CD44s and CD44v play overlapping or contradictory roles in tumor initiation and progression, which is not fully understood. Herein, we discuss the present understanding of the functional and structural roles of CD44 in the pathogenic mechanism of multiple cancers. The regulation functions of CD44 in cancers‐associated signaling pathways is summarized. Moreover, we provide an overview of the anticancer therapeutic strategies that targeting CD44 and preclinical and clinical trials evaluating the pharmacokinetics, efficacy, and drug‐related toxicity about CD44‐targeted therapies. This review provides up‐to‐date information about the roles of CD44 in neoplastic diseases, which may open new perspectives in the field of cancer treatment through targeting CD44.

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Section: Cd44 In Neoplastic Diseasesmentioning

confidence: 99%

CD44 and its implication in neoplastic diseases

Xu,

Bai,

Lan

et al. 2024

MedComm

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“…Thus, ABCB1 has become a widely-known source of and marker for chemoresistance (c.f. 219 ). ABCB1 also functions as a broad specificity lipid translocase ( 326 ).…”

Section: Candidate Innate Immune Genes At the Intersection Of Cancer ...mentioning

confidence: 99%

Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease

Yeyeodu,

Hanafi,

Webb

et al. 2024

Front. Endocrinol.

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Both cancer and cardio-metabolic disease disparities exist among specific populations in the US. For example, African Americans experience the highest rates of breast and prostate cancer mortality and the highest incidence of obesity. Native and Hispanic Americans experience the highest rates of liver cancer mortality. At the same time, Pacific Islanders have the highest death rate attributed to type 2 diabetes (T2D), and Asian Americans experience the highest incidence of non-alcoholic fatty liver disease (NAFLD) and cancers induced by infectious agents. Notably, the pathologic progression of both cancer and cardio-metabolic diseases involves innate immunity and mechanisms of inflammation. Innate immunity in individuals is established through genetic inheritance and external stimuli to respond to environmental threats and stresses such as pathogen exposure. Further, individual genomes contain characteristic genetic markers associated with one or more geographic ancestries (ethnic groups), including protective innate immune genetic programming optimized for survival in their corresponding ancestral environment(s). This perspective explores evidence related to our working hypothesis that genetic variations in innate immune genes, particularly those that are commonly found but unevenly distributed between populations, are associated with disparities between populations in both cancer and cardio-metabolic diseases. Identifying conventional and unconventional innate immune genes that fit this profile may provide critical insights into the underlying mechanisms that connect these two families of complex diseases and offer novel targets for precision-based treatment of cancer and/or cardio-metabolic disease.

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“…Patients with advanced GBC have an average overall survival (OS) time of 4–14 months. Even with surgical resection, most progress to a metastatic stage highly resistant to conventional chemotherapy [ 4 , 5 ]. Although palliative systemic therapy and surgery combined with adjuvant chemotherapy are currently the best options for improving clinical outcomes for GBC patients, they have not been sufficient to increase patient survival rates significantly [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Co-Expression of Immunohistochemical Markers MRP2, CXCR4, and PD-L1 in Gallbladder Tumors Is Associated with Prolonged Patient Survival

Tittarelli

Barría

Sanders

et al. 2023

Cancers

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Gallbladder cancer (GBC) is a rare pathology in Western countries. However, it constitutes a relevant health problem in Asia and Latin America, with a high mortality in middle-aged Chilean women. The limited therapeutic options for GBC require the identification of targetable proteins with prognostic value for improving clinical management support. We evaluated the expression of targetable proteins, including three epithelial tumor markers, four proteins associated with multidrug and apoptosis resistance, and eleven immunological markers in 241 primary gallbladder adenocarcinomas. We investigated correlations between tumor marker expression, the primary tumor staging, and GBC patients’ survival using automated immunohistochemistry, a semi-automatic method for image analysis, univariate and multivariate statistical analyses, and machine learning algorithms. Our data show a significant association between the expression of MRP2 (p = 0.0028), CXCR4 (p = 0.0423), and PD-L1 (p = 0.0264), and a better prognosis for patients with late-stage primary tumors. The expression of the MRP2/CXCR4/PD-L1 cluster of markers discriminates among short-, medium-, and long-term patient survival, with an ROC of significant prognostic value (AUC = 0.85, p = 0.0012). Moreover, a high MRP2/CXCR4/PD-L1 co-expression is associated with increased survival time (30 vs. 6 months, p = 0.0025) in GBC patients, regardless of tumor stage. Hence, our results suggest that the MRP2/CXCR4/PD-L1 cluster could potentially be a prognostic marker for GBC.

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

Cited by 7 publications

References 99 publications

CD44 and its implication in neoplastic diseases

CD44 and its implication in neoplastic diseases

Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease

Co-Expression of Immunohistochemical Markers MRP2, CXCR4, and PD-L1 in Gallbladder Tumors Is Associated with Prolonged Patient Survival

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