If small molecules immunotherapy comes, can the prime be far behind?

Zhang, Jingyu; Qu, Bingxue; Yang, Haiyan; Hu, Shengquan; Dong, Xiaowu

doi:10.1016/j.ejmech.2021.113356

Cited by 28 publications

(20 citation statements)

References 219 publications

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“…Therefore, the therapeutic effects of ICB on OV are still limited. The study on small molecule inhibitors to eliminate the limitations of mAbs is a new direction for ICB therapy ( Zhang et al, 2020 ; Zhang et al, 2021 ). More and more evidence showed that small molecule inhibitors that target oncogenic play a role far beyond the biological behavior of tumors.…”

Section: Disscussionmentioning

confidence: 99%

MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer

Wang

et al. 2022

Front. Genet.

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Background: Microchromosome maintenance protein 10 (MCM10) is required for DNA replication in all eukaryotes, and it plays a key role in the development of many types of malignancies. However, we currently still do not know the relationship between MCM10 and ovarian cancer (OV) prognosis and immune checkpoints.Methods: The Gene Expression Profiling Interactive Analysis and Tumor Immunology Estimation Resource (TIMER) databases were used to investigate MCM10 expression in Fan cancer. The Kaplan-Meier Plotter and PrognoScan were used to assess the relationship between MCM10 and OV prognosis. The LinkedOmics database was used to analyze the MCM10 co-expression network and explore GO term annotation and the KEGG pathway. The relationship between MCM10 expression and immune infiltration in OV was investigated using the Tumor Immunology Estimation Resource database. cBioPortal database was used to explore the relationship between MCM10 expression and 25 immune checkpoints. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect MCM10 expression. The prognosis was also analyzed by distinguishing between high and low expression groups based on median expression values.Results: The results of the three data sets (220,651_s_at, 222,962_s_at and 223,570_at) in KM Plotter all indicated that the overall survivalof the high MCM10 expression group was lower than that of the low expression group OV, and the results of GSE9891 also reached the same conclusion. The expression level of MCM10 was negatively correlated with B cells and CD8+T cells, and positively correlated with CD4+T Cells and Macrophages. GO term annotation and KEGG pathway analysis showed that the co-expressed genes of MCM10 were mainly enriched in cell cycle and DNA replication. The alterations in MCM10 coexisted statistically with the immune checkpoints CTLA4, TNFSF4, TNFSF18, CD80, ICOSLG, LILRB1 and CD200. PCR results displayed that MCM10 was highly expressed in OV tissues, and the increased expression of MCM10 was significantly associated with poor overall survival.Conclusion: These results demonstrated that high expression of MCM10 was associated with poor prognosis in OV and correlated with immune checkpoints.

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Section: Disscussionmentioning

confidence: 99%

MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer

Wang

et al. 2022

Front. Genet.

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“…These findings prompted novel pre-clinical and clinical therapeutic approaches targeting different adenosinergic signalling components and the whole purinome. Notable targets in these efforts have included CD39 [37,38], CD73 [13,39], CD38 [40], and A 2A R [41][42][43]. Other studies have focused on chimeric antigen receptor T (CAR-T) cells with A2AR suppression to block T-cell functionality [44,45] and on combination therapies targeting the above-mentioned proteins together with anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1) [46] or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) [47].…”

Section: Current Therapeutic Focusmentioning

confidence: 99%

Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?

Kotulová

Hajdúch

Džubák

2021

IJMS

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A key objective in immuno-oncology is to reactivate the dormant immune system and increase tumour immunogenicity. Adenosine is an omnipresent purine that is formed in response to stress stimuli in order to restore physiological balance, mainly via anti-inflammatory, tissue-protective, and anti-nociceptive mechanisms. Adenosine overproduction occurs in all stages of tumorigenesis, from the initial inflammation/local tissue damage to the precancerous niche and the developed tumour, making the adenosinergic pathway an attractive but challenging therapeutic target. Many current efforts in immuno-oncology are focused on restoring immunosurveillance, largely by blocking adenosine-producing enzymes in the tumour microenvironment (TME) and adenosine receptors on immune cells either alone or combined with chemotherapy and/or immunotherapy. However, the effects of adenosinergic immunotherapy are not restricted to immune cells; other cells in the TME including cancer and stromal cells are also affected. Here we summarise recent advancements in the understanding of the tumour adenosinergic system and highlight the impact of current and prospective immunomodulatory therapies on other cell types within the TME, focusing on adenosine receptors in tumour cells. In addition, we evaluate the structure- and context-related limitations of targeting this pathway and highlight avenues that could possibly be exploited in future adenosinergic therapies.

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“…In addition, chemotherapy drugs, which always show poor selectivity, can also easily kill a large number of normal cells, destroy the immune system and develop drug resistance [3]. Although immunotherapy is attracting increasing attention worldwide, it is still extremely expensive and may also be life-threatening if the anticancer immune responses are not well controlled [4,5]. Based on the current status of cancer therapy strategies, there is an urgent need to develop new technologies to combat cancer.…”

Section: Introductionmentioning

confidence: 99%

Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics

et al. 2021

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Cobalt is essential to the metabolism of all animals due to its key role in cobalamin, also known as vitamin B12, the primary biological reservoir of cobalt as an ultra-trace element. Current cancer treatment strategies, including chemotherapy and radiotherapy, have been seriously restricted by their side effects and low efficiency for a long time, which urges us to develop new technologies for more effective and much safer anticancer therapies. Novel nanotechnologies, based on different kinds of functional nanomaterials, have been proved to act as effective and promising strategies for anticancer treatment. Based on the important biological roles of cobalt, cobalt oxide nanoparticles (NPs) have been widely developed for their attractive biomedical applications, especially their potential for anticancer treatments due to their selective inhibition of cancer cells. Thus, more and more attention has been attracted to the preparation, characterization and anticancer investigation of cobalt oxide nanoparticles in recent years, which is expected to introduce novel anticancer treatment strategies. In this review, we summarize the synthesis methods of cobalt oxide nanoparticles to discuss the advantages and restrictions for their preparation. Moreover, we emphatically discuss the anticancer functions of cobalt oxide nanoparticles as well as their underlying mechanisms to promote the development of cobalt oxide nanoparticles for anticancer treatments, which might finally benefit the current anticancer therapeutics based on functional cobalt oxide nanoparticles.

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If small molecules immunotherapy comes, can the prime be far behind?

Cited by 28 publications

References 219 publications

MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer

MCM10 is a Prognostic Biomarker and Correlated With Immune Checkpoints in Ovarian Cancer

Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?

Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics

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