Review
Oncology
Kellen Wright, Thuc Ly, Matthew Kriet, Andras Czirok, Sufi Mary Thomas
Summary: Cancer cells rely on the tumor microenvironment (TME) for growth and metastasis. Among the components of TME, cancer-associated fibroblasts (CAFs) play a crucial role. CAFs are heterogeneous and can remodel the microenvironment, as well as communicate with immune cells to aid in immune evasion. This review focuses on the factors and signaling pathways of CAFs.
Review
Medicine, Research & Experimental
Jitang Chen, Ze-yang Ding, Si Li, Sha Liu, Chen Xiao, Zifu Li, Bi-xiang Zhang, Xiao-ping Chen, Xiangliang Yang
Summary: Targeting TGF beta signaling for cancer therapy presents challenges and opportunities, as inhibitors can enhance chemotherapy efficacy but must also consider the dual role of TGF beta in normal tissues and tumors to avoid unwanted side effects.
Review
Immunology
Dipranjan Laha, Robert Grant, Prachi Mishra, Naris Nilubol
Summary: The tumor microenvironment is a complex system consisting of various cells and structures. Tumor necrosis factor-alpha plays a crucial role in the TME, affecting the interaction between tumor cells and immune cells, with significant implications for immune response, tumorigenesis, invasion, and metastasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eiman Elwakeel, Andreas Weigert
Summary: Activation of the tumor-associated stroma and the role of cancer-associated fibroblasts (CAFs) in shaping tumor development are crucial in breast cancer. Understanding the multiple functions of CAFs and developing intervention strategies are important for improving breast cancer therapy. Further research is needed to identify specific subsets of CAFs that can be targeted for therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Maria V. Monteiro, Yu Shrike Zhang, Vitor M. Gaspar, Joao F. Mano
Summary: The combination of organ-on-a-chip platforms with additive manufacturing technologies offers a disruptive approach for upgrading cancer-on-a-chip systems. These hybrid platforms can create physiomimetic 3D models that better emulate tumor microenvironment elements and improve the predictability of therapeutics performance.
TRENDS IN BIOTECHNOLOGY
(2022)
Article
Oncology
Stefania D'Agostino, Lucia Tombolan, Mattia Saggioro, Chiara Frasson, Elena Rampazzo, Stefania Pellegrini, Francesca Favaretto, Carlo Biz, Pietro Ruggieri, Piergiorgio Gamba, Paolo Bonvini, Sanja Aveic, Roberto Giovannoni, Michela Pozzobon
Summary: The study demonstrates that unlike epithelial cancers, rhabdomyosarcoma (RMS) cells play a direct role in remodeling their own ECM and are less dependent on support from cancer-associated fibroblasts (CAFs). In both 2D and 3D models, the rate of interaction between RMS cells and fibroblasts is significantly lower, indicating a reduced reliance on CAFs for tumor growth.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Pradip De, Jennifer Aske, Nandini Dey
Summary: This review explores how cancer-associated fibroblasts interact with various cells in the tumor microenvironment to support the development of resistance to cancer therapy. Understanding the role of cancer-associated fibroblasts in treatment resistance is crucial for designing effective strategies to counteract drug resistance and improve treatment outcomes.
Review
Pharmacology & Pharmacy
Dan Liang, Lu Liu, Yunjie Zhao, Zhenyi Luo, Yadi He, Yanping Li, Shiyun Tang, Jianyuan Tang, Nianzhi Chen
Summary: The extracellular matrix (ECM) plays a crucial role in the tumor microenvironment (TME) and has become the focus of cancer research and treatment. Multiple cell signaling pathways in ECM remodeling contribute to uncontrolled cancer growth, metastasis, immune evasion, and drug resistance. Targeting ECM remodeling could be a novel strategy for different stages of cancer and overcoming drug resistance.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Klaudia Bonowicz, Klaudia Mikolajczyk, Inaz Faisal, Murtaz Qamar, Kerstin Steinbrink, Konrad Kleszczynski, Alina Grzanka, Maciej Gagat
Summary: Extracellular vesicles play a central role in communication between tumor and non-tumor cells. The function of the endothelial barrier and the receptors on its surface are important for these interactions. Inflammation and dysregulation of TGF-beta signaling are associated with tumor progression. This review aims to explore the correlation between EV release, TGF-beta-dependent inflammation, and dysregulation of downstream TGF-beta signaling in cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Yi Li, Changyuan Wang, Ting Huang, Xijie Yu, Bole Tian
Summary: Breast cancer deaths are primarily caused by metastasis. There are several treatment options, but limited options for preventing or inhibiting breast tumor metastases. Studies have focused on the importance of the tumor microenvironment (TME) in metastasis of breast cancer.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Siva Bharath Merugu, Bingjie Zhou, Hitesh Bhagavanbhai Mangukiya, Hema Negi, Raza Ghulam, Debmalya Roy, Sehar Qudsia, Zeling Wang, Dhahiri Saidi Mashausi, Fakhar-Un-Nisa Yunus, Guo-Song Liu, Dawei Li
Summary: AGR2 is often overexpressed in several types of cancer, and it can translocate into the cytoplasm through endocytosis when secreted by tumor cells or externally added. Extracellular AGR2 can bind to beta-catenin and promote its nuclear accumulation in fibroblasts and cancer cells, even in the presence of an EGFR inhibitor, suggesting an alternative pathway for beta-catenin regulation. The effects of extracellular AGR2 on beta-catenin were confirmed to be caused solely by AGR2 through experiments using a monoclonal antibody against AGR2.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Biotechnology & Applied Microbiology
Ming Jia, Dan Zhang, Chunxiang Zhang, Chunhong Li
Summary: Modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach, and nano-delivery systems have been developed to alter the TME. These systems change the microenvironment in various ways, including depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, and improving the hypoxic environment.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Oncology
Eva Andreuzzi, Albina Fejza, Maurizio Polano, Evelina Poletto, Lucrezia Camicia, Greta Carobolante, Giulia Tarticchio, Federico Todaro, Emma Di Carlo, Melania Scarpa, Marco Scarpa, Alice Paulitti, Alessandra Capuano, Vincenzo Canzonieri, Stefania Maiero, Mara Fornasarig, Renato Cannizzaro, Roberto Doliana, Alfonso Colombatti, Paola Spessotto, Maurizio Mongiat
Summary: This study reveals the importance of EMILIN-2 in the development and prognosis of colorectal cancer. Loss of EMILIN-2 is associated with increased tumor numbers and altered immune cell populations in CRC models. Mechanistically, EMILIN-2 regulates macrophage polarization through the Toll-like Receptor 4/MyD88/NF-kappa B pathway. Furthermore, EMILIN-2 expression levels are correlated with the prognosis of CRC patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Jagadeesh Janjanam, Glendin Pano, Ruishan Wang, Benjamin A. Minden-Birkenmaier, Hannah Breeze-Jones, Eleanor Baker, Cecile Garcin, Georgia Clayton, Abbas Shirinifard, Ana Maria Zaske, David Finkelstein, Myriam Labelle
Summary: This study identifies WISP2 as the first inhibitor of collagen linearization, which can normalize collagen architecture and inhibit metastasis by therapeutically restoring a high WISP2: WISP1 ratio.
Article
Oncology
Bian Yanes, Elena Rainero
Summary: Mitochondria play essential roles in cellular functions, and dysfunctions have been observed in cancer. The interaction between cancer cells and the extracellular matrix (ECM) is crucial for tumor initiation and progression. Remodeling of ECM associated with tumorigenesis contributes to the regulation of mitochondrial function, promoting cancer cell metabolic plasticity that fuels invasion and metastasis.
Article
Immunology
Ding-Li Yu, Zhi-Ping Lou, Feng-Yun Ma, Masoud Najafi
Summary: Interactions within the tumour microenvironment (TME) play a crucial role in cancer therapy. Paclitaxel, a commonly used chemotherapy drug, not only inhibits cell cycle but also modulates interactions in TME to suppress tumour growth. This review discusses the effects of paclitaxel on anti-tumour immunity, immunosuppressive cells, hypoxia, and angiogenesis, and suggests targeting these interactions to improve therapy efficiency.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Peyman Amini, Saeedeh Jafari Nodooshan, Milad Ashrafizadeh, Akbar Aliasgharzadeh, Zarichehr Vakili, Saeed Tavakoli, Tayebeh Aryafar, Ahmed Eleojo Musa, Masoud Najafi, Shahram Taeb, Bagher Farhood
Summary: In this study, imperatorin (IMP) was found to enhance the effectiveness of external radiotherapy (ERT) and hyperthermia (HT) in breast cancer cells by increasing the expression of pro-apoptotic genes and reducing the levels of the anti-apoptotic protein Bcl-2, leading to a decrease in cell viability.
CURRENT RADIOPHARMACEUTICALS
(2022)
Review
Immunology
Keywan Mortezaee, Jamal Majidpoor
Summary: Tumor-associated macrophages (TAMs) are immune cells that infiltrate tumor areas and have intense interactions with other cells. The metabolic abnormalities in tumors can affect the polarization of macrophages towards pro-tumor or anti-tumor phenotypes. Adjusting the metabolic systems of macrophages can be an effective tool in cancer therapy.
INTERNATIONAL REVIEWS OF IMMUNOLOGY
(2023)
Review
Cell Biology
Xiao-yu Wu, Wen-Wen Xu, Xiang-kun Huan, Guan-nan Wu, Gang Li, Yu-Hong Zhou, Masoud Najafi
Summary: Resistance of cancer cells to anti-tumour agents is a major challenge in cancer treatment. Metformin, an antidiabetic drug, can enhance cell death mechanisms and play a key role in inducing cell death, thereby increasing the therapeutic efficiency of anti-cancer therapy.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Masoud Moslehi, Sepideh Rezaei, Pourya Talebzadeh, Mohammad Javed Ansari, Mohammed Abed Jawad, Abduladheem Turki Jalil, Nima Rastegar-Pouyani, Emad Jafarzadeh, Shahram Taeb, Masoud Najafi
Summary: The incidence of cancer is increasing globally. The long-term adverse effects of cancer therapy and tumor resistance to anticancer agents are major concerns. Apigenin, a plant-derived molecule, has potential as an adjuvant for chemoprevention and overcoming malignancy resistance to cancer therapy. It has promising anti-tumor effects and may reduce genomic instability and risks of second malignancies in normal tissues, as well as improve the efficacy of anticancer modalities.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2023)
Review
Cell Biology
Keywan Mortezaee, Jamal Majidpoor
Summary: The low frequency of durable responses in patients treated with immune checkpoint inhibitors (ICIs) requires additional strategies to enhance immune responses against cancer. Transforming growth factor-beta (TGF-beta) is a cytokine often expressed in tumors and promotes an immunosuppressive tumor microenvironment (TME). TGF-beta also influences the efficacy of anti-PD-1/PD-L1 therapy. Combining TGF-beta inhibitors with anti-PD(L)1 has shown promising results, and clinical trials are currently underway to investigate the use of agents with bifunctional capacity and fusion proteins to reinvigorate immune responses against advanced stage cancers, particularly those with an immunologically cold ecosystem.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Review
Immunology
Arian Charehjoo, Jamal Majidpoor, Keywan Mortezaee
Summary: Metabolic alterations occur commonly in tumor cells to adapt energetic sources for proliferation, survival, and resistance. IDO1 is an enzyme that degrades tryptophan and its upregulation in cancer stroma impacts immune tolerance and cancer evasion. IDO1 inhibitors combined with immune checkpoint inhibitors show promise in treating advanced solid tumors and overcoming ICI therapy bypass.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Keywan Mortezaee
Summary: B7x is a co-inhibitory molecule highly expressed in non-inflamed cancers, contributing to cancer progression and poor outcomes. It hampers peripheral immune responses and promotes immunosuppressive cells and regulatory T cells in cancer. Evaluation of B7x in sera is a potential biomarker for cancer patient response. B7x overexpression is involved in tumor resistance to immune checkpoint inhibitor therapy, but anti-B7x treatment can reinvigorate exhausted T cells and complement conventional ICI therapy. The development of bispecific antibodies against B7x and other regulatory molecules is an advance in the field.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Instruments & Instrumentation
Sajad Najafi, Jamal Majidpoor, Keywan Mortezaee
Summary: Extracellular vesicles (EVs) are membrane-bound organelles released from eukaryotic cells that can be used as biomarkers for human diseases. EVs have favorable features as ideal drug carriers and vaccines for diseases including cancer.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Review
Multidisciplinary Sciences
Keywan Mortezaee, Jamal Majidpoor
Summary: This review discusses the impact of mono or combination therapy of immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients, comparing clinical outcomes and safety. Cancer subtype, tumor mutational burden (TMB), programmed death-ligand 1 (PD-L1) expression state and T cell infiltration (TIL) density are considered for interpretations. Besides, current progresses in the field of immunotherapy are discussed.
Article
Medicine, Research & Experimental
Sajad Najafi, Keywan Mortezaee
Summary: Traditionally, vaccines have played a crucial role in eradicating infectious diseases and saving millions of lives. However, the development of anticancer vaccines faces challenges and requires further optimization. Dendritic cells, as the most potent antigen presenting cells, have been used in tumor immunotherapies but their efficacy needs improvement.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pathology
Sasan Parvini, Jamal Majidpoor, Keywan Mortezaee
Summary: This review focuses on the impact of PD-L1 on combo nivolumab-ipilimumab therapy in advanced solid cancer patients, indicating that patient responses can be affected by different levels of PD-L1 expression. Variations in responses are observed among different cancer types or doses of immunotherapy drugs. Therefore, relying solely on PD-L1 as a biomarker may not be reliable for predicting the clinical efficacy of combo nivolumab-ipilimumab. Other biomarkers or a combination of PD-L1 with other factors should be considered for predicting patient responses.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Oncology
Keywan Mortezaee, Jamal Majidpoor
Summary: Extracellular vesicles (EVs), particularly exosomes, play a crucial role in the communication and signal transmission between tumor cells and the tumor microenvironment (TME). Hypoxia, a characteristic of TME, stimulates tumor cells to release more EVs, which transfer biological information to promote hypoxia and hypoxia inducible factor (HIF) functionality. The EVs secreted under hypoxic conditions carry pro-tumorigenic factors that contribute to various tumor-related processes including cancer cell proliferation and survival, immune escape, angiogenesis, invasion, metastasis, and therapy resistance. This review focuses on the interplay between hypoxia and EVs, particularly exosomes, and their impact on key hallmarks of cancer.
Review
Oncology
Keywan Mortezaee, Jamal Majidpoor
Summary: NK cells, as lymphoid cells of innate immunity, play important roles in immune surveillance and immunotherapy. However, the decreased cytotoxic activity and reduced number of activating receptors limit their application in cellular immunotherapy.
Article
Radiology, Nuclear Medicine & Medical Imaging
Daryoush Khoramian, Soroush Sistani, Bagher Farhood
Summary: The study measured systematic and random set-up errors in prostate cancer radiotherapy using EPID and proposed the optimum CTV-to-PTV margin. Results showed population systematic and random errors in different directions, leading to calculated margins based on different formulas, with overall margins averaging at 2.73, 4.98 and 5.86 mm.
JOURNAL OF RADIOTHERAPY IN PRACTICE
(2022)