Prostate tumor RON receptor signaling mediates macrophage recruitment to drive androgen deprivation therapy resistance through Gas6‐mediated Axl and RON signaling

Brown, Nicholas E.; Jones, Angelle; Hunt, Brian G.; Waltz, Susan E.

doi:10.1002/pros.24416

Cited by 7 publications

(4 citation statements)

References 45 publications

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“…As described previously, RON overexpression in PCa cells enhances CCL2 production for macrophage recruitment and RON-overexpressing tumors alter macrophage state to drive growth under androgen-deprived conditions. It is therefore plausible that combining RON inhibition with macrophage depletion promotes CRPC sensitization to ADT [ 169 ]. Coincidentally, anti CCR2 antagonist could reduce the side effects induced by ADT, although single antibody targeting CCL2 failed in a phase II clinical trial [ 170 ].…”

Section: Promising Strategies For Pca Treatment Via Targeting Tamsmentioning

confidence: 99%

The Roles of Tumor-Associated Macrophages in Prostate Cancer

Han

Deng

et al. 2022

Journal of Oncology

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The morbidity of prostate cancer (PCa) is rising year by year, and it has become the primary cause of tumor-related mortality in males. It is widely accepted that macrophages account for 50% of the tumor mass in solid tumors and have emerged as a crucial participator in multiple stages of PCa, with the huge potential for further treatment. Oftentimes, tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) behave like M2-like phenotypes that modulate malignant hallmarks of tumor lesions, ranging from tumorigenesis to metastasis. Several clinical studies indicated that mean TAM density was higher in human PCa cores versus benign prostatic hyperplasia (BPH), and increased biopsy TAM density potentially predicts worse clinicopathological characteristics as well. Therefore, TAM represents a promising target for therapeutic intervention either alone or in combination with other strategies to halt the “vicious cycle,” thus improving oncological outcomes. Herein, we mainly focus on the fundamental aspects of TAMs in prostate adenocarcinoma, while reviewing the mechanisms responsible for macrophage recruitment and polarization, which has clinical translational implications for the exploitation of potentially effective therapies against TAMs.

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Section: Promising Strategies For Pca Treatment Via Targeting Tamsmentioning

confidence: 99%

The Roles of Tumor-Associated Macrophages in Prostate Cancer

Han

Deng

et al. 2022

Journal of Oncology

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“…Prostate tumor-associated macrophages can promote the growth of PCa, and secreted Gas6 can further enhance the activation of RON and AXL receptors in PCa cells, thereby driving CRPC. Targeting RON and macrophages promotes CRPC sensitivity to ADT ( 52 ). Targeting the CSF1 receptor can also reverse macrophage-mediated resistance to androgen blockade in PCa ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer

Wang

Pan

et al. 2023

Front. Endocrinol.

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BackgroundProstate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance.MethodsThe data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups.ResultsTwo drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein–protein interaction network identified 10 hub genes in the brown module LUC7L3, SNRNP70, PRPF3, LUC7L, CLASRP, CLK1, CLK2, U2AF1L4, NXF1, and THOC1) and 13 in the yellow module (PNN, PPWD1, SRRM2, DHX35, DMTF1, SALL4, MTA1, HDAC7, PHC1, ACIN1, HNRNPH1, DDX17, and HDAC6). The prognostic model composed of RNF207, REC8, DFNB59, HOXA2, EPOR, PILRB, LSMEM1, TCIRG1, ABTB1, ZNF276, ZNF540, and DPY19L2 could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy.ConclusionIn this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.

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“…NRP1, serving as a key factor of SARS-CoV-2 virus infection (41), could increase the susceptibility of cancer patients to SARS-CoV-2 virus and targeting (42), and its overexpression is associated with poor prognosis in bladder cancer cells and hepatocellular carcinoma, and inhibiting its expression could promote tumor cell apoptosis (43,44). In addition, the increased expression of SCARB1 could promote cell transformation towards malignancy of clear cell renal cell carcinoma leading to poor prognosis of patients (45), while the over-expression of AXL could accelerate EGFR mutation and promote the metastasis, invasion or drug resistance of tumors such as lung cancer (46), colorectal cancer (47), pancreatic cancer (48) and prostate tumor (49). Then, genetic and epigenetic studies have also shown that high frequencies of SNV, and methylation were noted in these five STGs, which may impact STGs expression in malignancies and affect the prognosis of cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals genomic, clinical and immunological features of SARS-CoV-2 virus target genes in pan-cancer

Liao

Wang²,

Zou³

et al. 2023

Front. Immunol.

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The SARS-CoV-2 virus, also known as the severe acute respiratory syndrome coronavirus 2, has raised great threats to humans. The connection between the SARS-CoV-2 virus and cancer is currently unclear. In this study, we thus evaluated the multi-omics data from the Cancer Genome Atlas (TCGA) database utilizing genomic and transcriptomic techniques to fully identify the SARS-CoV-2 target genes (STGs) in tumor samples from 33 types of cancers. The expression of STGs was substantially linked with the immune infiltration and may be used to predict survival in cancer patients. STGs were also substantially associated with immunological infiltration, immune cells, and associated immune pathways. At the molecular level, the genomic changes of STGs were frequently related with carcinogenesis and patient survival. In addition, pathway analysis revealed that STGs were involved in the control of signaling pathways associated with cancer. The prognostic features and nomogram of clinical factors of STGs in cancers have been developed. Lastly, by mining the cancer drug sensitivity genomics database, a list of potential STG-targeting medicines was compiled. Collectively, this work demonstrated comprehensively the genomic alterations and clinical characteristics of STGs, which may offer new clues to explore the mechanisms on a molecular level between SARS-CoV-2 virus and cancers as well as provide new clinical guidance for cancer patients who are threatened by the COVID-19 epidemic.

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Prostate tumor RON receptor signaling mediates macrophage recruitment to drive androgen deprivation therapy resistance through Gas6‐mediated Axl and RON signaling

Cited by 7 publications

References 45 publications

The Roles of Tumor-Associated Macrophages in Prostate Cancer

The Roles of Tumor-Associated Macrophages in Prostate Cancer

Identification of bicalutamide resistance-related genes and prognosis prediction in patients with prostate cancer

Multi-omics analysis reveals genomic, clinical and immunological features of SARS-CoV-2 virus target genes in pan-cancer

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