Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 93, P. 101205 - 101205

Published: July 27, 2023

Anthracyclines have been important and effective treatments against a number of cancers since their discovery. However, use in therapy has complicated by severe side effects toxicity that occur during or after treatment, including cardiotoxicity. The mode action anthracyclines is complex, with several mechanisms proposed. It possible high due to the large set processes involved anthracycline action. development resistance major barrier successful treatment when using anthracyclines. This based on series studied addressed recent years. work provides an overview used cancer therapy. discusses activity, toxicity, chemoresistance, as well approaches improve decrease overcome resistance.

Language: Английский

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Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10509 - 10509

Published: Sept. 10, 2022

The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of ECM, are greatly remodeled alongside development. More and more studies have confirmed that collagens changed from barrier to providing assistance In this course, cause remodeling progression, which turn, promotes interaction between tumor cells complex with biochemical mechanical signals intervention through activating diverse signal pathways. As mechanism gradually clears, it becomes new target find opportunities diagnose treat cancer. review, we investigated process collagen progression discussed cells. Several typical effects associated were highlighted such fibrillation precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, guiding invasion. Then, values diagnosis prognosis focused on. It worth noting several generated fragments serum reported be able biomarkers for prognosis, beneficial clinic detection. At glance, variety summarized. Many collagen-associated targets drugs been treatment recent years. related review. mass data collected classified by mechanism. Overall, complicated, mechanisms not completely clear. A lot excavated diagnosis. However, therapeutic almost clinical trials, merely few applications. So, efforts needed collagens-associated drug development research treatment.

Language: Английский

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Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative “cold” triple-negative breast cancer

Bioactive Materials, Journal Year: 2023, Volume and Issue: 25, P. 61 - 72

Published: Jan. 22, 2023

Triple-negative breast cancer (TNBC) due to lack of clear target and notorious "cold" tumor microenvironment (TME) is one the most intractable lethal malignancies. Tuning TME into "hot" becomes an emerging therapeutic strategy TNBC. Herewith, we report that integrin-targeting micellar gemcitabine paclitaxel (ATN-mG/P, ATN sequence: Ac-PhScNK-NH2) cooperating with polymersomal CpG (NanoCpG) effectively "heated up" treated ATN-mG/P exhibited greatly boosted apoptotic activity in 4T1 cells, induced potent immunogenic cell death (ICD), efficiently stimulated maturation bone marrow-derived dendritic cells (BMDCs). Remarkably, a postoperative TNBC model, combining NanoCpG promoted strong anti-cancer immune responses, showing augmented proportion mature DCs CD8+ T while reduced immune-suppressive myeloid-derived suppressor (MDSCs) regulatory (Treg), which led complete inhibition lung metastasis 60% mice tumor-free. The co-delivery at desired ratio combination provides unique platform for chemoimmunotherapy tumors like

Language: Английский

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In Situ Tumor Vaccine for Lymph Nodes Delivery and Cancer Therapy Based on Small Size Nanoadjuvant

Small, Journal Year: 2023, Volume and Issue: 19(33)

Published: April 20, 2023

Tumor vaccine is a promising cancer treatment modality, however, the convenient antigens loading in vivo and efficient delivery of vaccines to lymph nodes (LNs) still remain formidable challenge. Herein, an situ nanovaccine strategy targeting LNs induce powerful antitumor immune responses by converting primary tumor into whole-cell then delivering these nanoadjuvants simultaneously proposed. The based on hydrogel system, which loaded with doxorubicin (DOX) nanoadjuvant CpG-P-ss-M. gel system exhibits ROS-responsive release DOX CpG-P-ss-M, generating abundant storage antigens. CpG-P-ss-M adsorbs through positive surface charge achieves reversal, forming small-sized negatively charged situ, are primed LNs. Eventually, promotes uptake dendritic cells (DCs), maturation DCs, proliferation T cells. Moreover, combined anti-CTLA4 antibody losartan inhibits growth 50%, significantly increasing percentage splenic cytotoxic (CTLs), tumor-specific responses. Overall, effectively induces response. This study provides scalable for vaccination.

Language: Английский

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The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Oct. 27, 2023

The renin-angiotensin-aldosterone system (RAAS), is an old with new fundamental roles in cancer biology which influences cell growth, migration, death, and metastasis. RAAS signaling enhances proliferation malignancy directly indirectly by affecting tumor cells modulating angiogenesis. Cancer development may be influenced the balance between ACE/Ang II/AT1R ACE2/Ang 1-7/Mas receptor pathways. interactions Ang I/AT2R as well Ang1-7/Mas alamandine/MrgD receptors pathway can significantly impact of cancer. I/AT2R, Ang1-7/Mas, have anticancer effects while involved Evidence suggests that inhibitors RAAS, are conventionally used to treat cardiovascular diseases, beneficial therapies.Herein, we aim provide a thorough description elements their molecular play Alongside this, role components sex-dependent cancers GI will discussed hope enlightening venues for adjuvant treatment.

Language: Английский

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The impact of tumor microenvironment: unraveling the role of physical cues in breast cancer progression

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(2), P. 823 - 844

Published: Jan. 19, 2024

Abstract Metastasis accounts for the vast majority of breast cancer-related fatalities. Although contribution genetic and epigenetic modifications to cancer progression has been widely acknowledged, emerging evidence underscores pivotal role physical stimuli in driving metastasis. In this review, we summarize changes mechanics microenvironment describe various forces that impact migrating circulating tumor cells throughout metastatic process. We also discuss mechanosensing mechanotransducing molecules responsible promoting malignant phenotype cells. Gaining a comprehensive understanding mechanobiology carries substantial potential propel progress prognosis, diagnosis, patient treatment.

Language: Английский

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Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 4533 - 4568

Published: May 1, 2024

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy high potential in treating several cancers but its efficacy is limited as monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used Therefore, identifying their involvement and synergy CIT approaches decisive. Nano-based drug delivery systems (NDDSs) are ideal because they can simultaneously target immune cells cells, promoting accumulation, reducing the toxicity drug. In this review, we first introduce five current immunotherapies, including checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), vaccines, oncolytic virus (OVT) cytokine therapy. Subsequently, immunomodulatory effects chemotherapy by inducing immunogenic death (ICD), tumor killer infiltration, down-regulating immunosuppressive inhibiting checkpoints have described. Finally, NDDSs-mediated collaborative introduced detail, development nanoparticles prospected.

Language: Английский

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Biomaterials to regulate tumor extracellular matrix in immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 149 - 166

Published: Oct. 11, 2024

Language: Английский

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Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity its various subtypes. This study aimed to investigate differential expression genes and miRNAs involved in PI3K/AKT/mTOR signaling pathway, critical regulator progression. We analyzed tumor tissues from five breast subtypes-luminal A, luminal B HER2-negative, HER2-positive, triple-negative (TNBC)-and compared them with non-cancerous tissues. Microarray qRT-PCR techniques were employed profile mRNAs miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed statistical significance threshold (p) < 0.05. identified several upregulated across all subtypes, TNBC HER2-positive cancers showing most significant changes. Key such as COL1A1, COL4A1, PIK3CA, PIK3R1, mTOR found be overexpressed, correlating increased aggressiveness. miRNA revealed that miR-190a-3p, miR-4729, miR-19a-3p potentially regulate these genes, influencing pathway. For instance, reduced miR-190a-3p may contribute overexpression PIK3CA other pathway components, enhancing metastatic potential. Our findings suggest regulators play crucial roles progression, particularly aggressive subtypes like TNBC. The hold potential biomarkers for diagnosis treatment, but further validation functional studies is required. provides foundation targeted therapies at modulating this improve outcomes.

Language: Английский

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