Review
Pharmacology & Pharmacy
Yi Xiao, Dihua Yu
Summary: This article summarizes the current progress in targeting the tumor microenvironment in both drug development and clinical trials, emphasizing the challenges in intervening in the tumor microenvironment and discussing strategies to maximize therapeutic benefits. New technologies and approaches to better understand the tumor microenvironment are explored in this context.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Immunology
Sarah Jaboury, Kenny Wang, Kim Maree O'Sullivan, Joshua Daniel Ooi, Gwo Yaw Ho
Summary: Neutrophil Extracellular Traps (NETs) are a form of pro-inflammatory cell death characterized by the release of DNA webs containing bactericidal enzymes. NETosis plays a role in autoimmune diseases and cancer, causing tissue damage and promoting tumor growth. This mini-review summarizes the interaction between neutrophils, particularly NETosis, and cancer cells, highlighting potential targets for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
Yihui Yang, Liwen Ren, Wan Li, Yizhi Zhang, Sen Zhang, Binbin Ge, Hong Yang, Guanhua Du, Bo Tang, Hongquan Wang, Jinhua Wang
Summary: GABA is a common inhibitory neurotransmitter in the central nervous system of vertebrates, and recent studies have shown its involvement in tumor development and immune regulation. This review summarizes the role of GABAergic signaling in tumor proliferation, metastasis, progression, stemness, and the tumor microenvironment, as well as the underlying molecular mechanisms. The therapeutic advances in targeting GABA receptors for cancer treatment, particularly immunotherapy, are also discussed.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Hanshu Yuan, Justin Pratte, Charles Giardina
Summary: Ferroptosis is a recently defined form of programmed cell death that is distinct due to its iron dependency and accumulation of lipid hydroperoxides. It can be regulated by various cellular variables and is potentially linked to degenerative diseases and acute injury scenarios. Additionally, ferroptosis may have significance in tumor-suppression and cancer therapy as a proposed target.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jicheng Zhang, Hanlin Yin, Qiangda Chen, Guochao Zhao, Wenhui Lou, Wenchuan Wu, Ning Pu
Summary: Basophils, previously overlooked, have been found to potentially play a role in cancer development, with their function as tumor-protecting or tumor-promoting components still being debated and possibly dependent on tumor biology and the microenvironment.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2021)
Review
Oncology
Upasana Ray, Christopher L. Pathoulas, Prabhu Thirusangu, James W. Purcell, Nagarajan Kannan, Viji Shridhar
Summary: Abundant fibrotic stroma is a common feature in solid tumors, and targeting the tumor stroma, including the overexpressed LRRC15 protein, has become a promising therapeutic strategy. Effective LRRC15-targeted therapy may improve outcomes for patients with LRRC15-positive tumors, offering personalized clinical benefits and predictive biomarkers for preclinical assessment.
Review
Oncology
Liya Zhu, Xiu Juan Li, Prakash Gangadaran, Xiuli Jing, Byeong-Cheol Ahn
Summary: Macrophages play a significant role in the tumor microenvironment and have dual effects on the development of thyroid cancer. M1-like macrophages have cytotoxic effects on tumor cells and activate immune cells in the early stages of cancer, while M2-like macrophages promote tumor progression.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Xing Wang, Guobing Yin, Wei Zhang, Kunlin Song, Longbin Zhang, Zufeng Guo
Summary: PTGR1, a rate-limiting enzyme in the arachidonic acid metabolism pathway, is crucial in regulating the deactivation of eicosanoids like prostaglandins and leukotriene B4, making it a promising target for cancer therapy. Current research has focused on understanding PTGR1's role in cancer, potential inhibitors, and strategies for future research and therapeutics development.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Naji Kharouf, Thomas W. Flanagan, Sofie-Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah-Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
Summary: As a solid tumor, melanoma is composed of tumor cells, supporting stroma, extracellular matrix, and soluble molecules forming the tumor microenvironment. The tumor microenvironment plays a central role in tumor progression and treatment resistance, making it a potential target for melanoma treatment.
Review
Biochemistry & Molecular Biology
Surendra Kumar Sagar
Summary: This review focuses on the function of miR-106b and its downstream targets in cancer, providing insights into how miR-106b regulates cancer cell proliferation, migration, invasion, and metastasis by modulating tumor suppressor genes. The potential of miR-106b as a candidate for detection, diagnosis, and prognosis assessment in different cancer types is highlighted.
Review
Oncology
Mengfang Liu, Na Liu, Jinlei Wang, Shengqiao Fu, Xu Wang, Deyu Chen
Summary: Acetyl-CoA Synthetase 2 (ACSS2) is highly expressed in various tumors and plays an important role in tumor growth, proliferation, invasion, and metastasis under nutritional stress. ACSS2 inhibitors have shown effectiveness in halting cancer growth and can be used in combination with other antineoplastic drugs to reduce drug resistance. This article reviews the mechanisms of ACSS2-promoting tumor growth and the potential clinical application of targeted inhibitors.
Review
Oncology
Giulia Marelli, Nicolo Morina, Federica Portale, Marta Pandini, Marta Iovino, Giusy Di Conza, Ping-Chih Ho, Diletta Di Mitri
Summary: Macrophages are key players in the immune system and their dysfunction can contribute to various diseases, including cancer. Lipid metabolism plays a role in macrophage activation and lipid accumulation can lead to pathogenic features. A subset of lipid-loaded macrophages, known as tumor-associated macrophages (TAMs), are involved in tumor growth and immune suppression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Research & Experimental
Md Abdus Subhan, Vladimir P. Torchilin
Summary: This review elucidates the dual function of neutrophils in cancer treatment, highlighting their potential for drug delivery and targeting in pre-clinical models.
Review
Oncology
Weizhu Zhao, Haiying Yang, Jie Chai, Ligang Xing
Summary: The transcription factor RUNX2 plays a crucial role in the differentiation of bone marrow mesenchymal stem cells into osteoblasts and also in the invasion and metastasis of cancers. Due to its complex regulatory mechanisms, the specific role of RUNX2 in the occurrence, development, and prognosis of malignant tumors is not fully understood. It has emerged as a promising therapeutic target in cancer research.
CANCER MANAGEMENT AND RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Yinnan Chen, Quanpeng Qiu, Junjun She, Jun Yu
Summary: Extrachromosomal circular DNA (ecDNA) is highly prevalent in various cancers, including colorectal cancer (CRC), and plays a critical role in regulating oncogene expression and resistance to therapy. Understanding the mechanisms and features of ecDNA in CRC provides insights into its pathogenesis and potential diagnostic and therapeutic implications. This review discusses the biogenesis, distinct features, and functional roles of ecDNA in CRC, including its involvement in oncogene overexpression, gene regulation, and topological interactions with active chromatin.
Article
Oncology
Yin Wu, Dhruva Biswas, Charles Swanton
Summary: Intratumour heterogeneity (ITH) can affect the response of patients to immune checkpoint inhibitor (CPI) therapy, confounding the accuracy of predictive biomarkers and playing a role in both immune surveillance and immune evasion. A deeper understanding of the interaction between ITH and the immune system can potentially increase the proportion of patients experiencing durable responses from CPI therapy.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Pietro Andrei, Paolo Battuello, Gaia Grasso, Emanuele Rovera, Nicolo Tesio, Alberto Bardelli
Summary: Colorectal cancer is a common malignancy with a need for improved prevention and treatment. Although much research has been done, traditional chemotherapy remains the primary treatment for metastatic colorectal cancer. Therefore, there is a growing need for personalized therapies using emerging approaches like genomics and transcriptomics.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Oncology
G. Middleton, H. Robbins, F. Andre, C. Swanton
Summary: Based on the results from several platform studies, it has been concluded that genotype-matched therapy is effective for cancer patients, but there are still challenges in combination therapy. Precision medicine holds great promise in cancer treatment, but more accurate models are needed to capture the genomic complexity of human diseases.
ANNALS OF ONCOLOGY
(2022)
Review
Oncology
Gianluca Mauri, Pietro Paolo Vitiello, Alberto Sogari, Giovanni Crisafulli, Andrea Sartore-Bianchi, Silvia Marsoni, Salvatore Siena, Alberto Bardelli
Summary: Colorectal cancer is a prevalent and deadly cancer, and there is a clinical need for better patient selection for systemic treatments. Genotyping circulating tumour DNA is a potential method to personalize treatment and overcome limitations of traditional biopsy approaches. This review summarizes the evidence of ctDNA applicability in colorectal cancer and discusses ongoing clinical trials.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Erika Durinikova, Nicole M. Reilly, Kristi Buzo, Elisa Mariella, Rosaria Chila, Annalisa Lorenzato, Joao M. L. Dias, Gaia Grasso, Federica Pisati, Simona Lamba, Giorgio Corti, Andrea Degasperi, Carlotta Cancelliere, Gianluca Mauri, Pietro Andrei, Michael Linnebacher, Silvia Marsoni, Salvatore Siena, Andrea Sartore-Bianchi, Serena Nik-Zainal, Federica Di Nicolantonio, Alberto Bardelli, Sabrina Arena
Summary: In colorectal cancer, a subset of cases refractory to current therapies may benefit from inhibitors of DDR pathways and replication stress. By analyzing multiple biomarkers, colorectal cancers likely to respond to ATRi can be identified.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Margherita Pergolizzi, Laura Bizzozero, Federica Maione, Elena Maldi, Claudio Isella, Marco Macagno, Elisa Mariella, Alberto Bardelli, Enzo Medico, Caterina Marchio, Guido Serini, Federica Di Nicolantonio, Federico Bussolino, Marco Arese
Summary: This study revealed that NLGN1 is expressed in human colorectal tumors and promotes CRC cell migration and metastasis. Mechanistically, NLGN1 promotes the localization of APC to the cell membrane, stimulates beta-catenin translocation to the nucleus, and induces an EMT phenotype in CRC cell lines. This novel finding suggests NLGN1 as a potential therapeutic target for CRC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl H. Latimer, Mustasin Rassel, Dary Griffin, Lyndsey Hanson, Alberto Bardelli, Frederica Di Nicolantonio, Simon S. McDade, Christopher J. Scott, Shauna Lambe, Manisha Maurya, Andreas U. Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
Summary: Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant colorectal cancer. In this study, researchers found that the combination of AZ'1569 and a Bcl-xL inhibitor led to a dramatic and universal apoptosis, suggesting a potential therapeutic strategy for patients with KRAS G12C-mutant colorectal cancer.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Oncology
Vito Amodio, Simona Lamba, Rosaria Chila, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchio, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli
Summary: Patients with DNA mismatch repair deficiency (MMRd) in colorectal cancer (CRC) often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. MMRp CRCs with variable fractions of MMRd cells may impact immune surveillance. Modulation of the MMRd fraction in MMR heterogeneous tumors can enhance their immunogenicity.
Article
Pathology
Enrico Berrino, Maria Costanza Aquilano, Emanuele Valtorta, Vito Amodio, Giovanni Germano, Marco Gusmini, Katiuscia Gizzi, Elisabetta Fenocchio, Anna Sapino, Silvia Marsoni, Andrea Sartore-Bianchi, Alberto Bardelli, Salvatore Siena, Emanuela Bonoldi, Caterina Marchio
Summary: Colorectal cancer cells often exhibit homogeneous retention or loss of mismatch repair (MMR) protein expression, but rare cases show heterogeneous patterns. In this study, 200 colorectal cancers were analyzed for MMR protein expression, resulting in three groups: proficient MMR, deficient MMR, and heterogeneous MMR expression. Heterogeneous MMR tumors were further examined and compared to the other groups, revealing differential gene expression patterns and increased tumor-infiltrating lymphocytes.
Article
Oncology
Gianluca Mauri, Giorgio Patelli, Viviana Gori, Calogero Lauricella, Benedetta Mussolin, Alessio Amatu, Katia Bencardino, Federica Tosi, Erica Bonazzina, Emanuela Bonoldi, Alberto Bardelli, Salvatore Siena, Andrea Sartore-Bianchi
Summary: The MAP2K1 K57N mutation has been identified as a resistance mechanism to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients. Avoiding the administration of these drugs to mCRC patients with the MAP2K1 N57K mutation is suggested.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Erica Torchiaro, Consalvo Petti, Sabrina Arena, Francesco Sassi, Giorgia Migliardi, Alfredo Mellano, Roberta Porporato, Marco Basirico, Loretta Gammaitoni, Enrico Berrino, Monica Montone, Giorgio Corti, Giovanni Crisafulli, Caterina Marchio, Alberto Bardelli, Enzo Medico
Summary: High-grade mucinous colorectal cancer (HGM CRC) is an aggressive subtype that is difficult to treat, often accompanied by signet ring cancer cells. The development of patient-derived preclinical models for this subtype is crucial in oncology. In this study, successful propagation of preclinical models from a Lynch syndrome patient with refractory HGM CRC was achieved, providing a valuable tool for exploring alternative treatments. Inhibition of the proteasome by bortezomib and the NEDD8 pathway by pevonedistat showed promising results in both in vitro and in vivo testing, highlighting their potential as effective therapeutic approaches against Lynch syndrome-associated HGM CRC.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Valentina Comunanza, Chiara Gigliotti, Simona Lamba, Gabriella Doronzo, Edoardo Vallariello, Valentina Martin, Claudio Isella, Enzo Medico, Alberto Bardelli, Dario Sangiolo, Federica Di Nicolantonio, Federico Bussolino
Summary: The introduction of targeted therapies has greatly improved the treatment of BRAFV600E melanoma, but acquired resistance remains a challenge. This study explored the strategy of VEGFA/BRAF inhibition in immunocompetent melanoma murine models and found that it reshaped the tumor microenvironment, enhanced immune cell infiltration, and sensitized tumors to immune checkpoint blockade. Combining VEGFA/BRAF targeting with anti-PD-1 antibody resulted in a durable response and complete tumor eradication in 50% of the mice.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Federica Di Nicolantonio, Alberto Bardelli
Summary: Allele-specific inhibitors of KRAS(G12C) have been approved for non-small-cell lung cancer. This article discusses recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRAS(G12C)-mutant metastatic colorectal cancer. The combination treatment showed promising efficacy and, if confirmed in later-phase trials, simultaneous inhibition of EGFR and KRAS(G12C) will introduce a new paradigm in precision oncology.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Marta Falcinelli, Giulia Dell'Omo, Elena Grassi, Elisa Mariella, Simonetta Maria Leto, Sharon Scardellato, Annalisa Lorenzato, Sabrina Arena, Andrea Bertotti, Livio Trusolino, Alberto Bardelli, Fabrizio d'Adda di Fagagna
Summary: This study found that colorectal cancer (CRC) does not easily engage in alternative lengthening of telomeres (ALT), even with mutations in ATRX and/or DAXX genes.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Subramanian Venkatesan, Mihaela Angelova, Jirina Bartkova, Samuel F. Bakhoum, Jiri Bartek, Nnennaya Kanu, Charles Swanton
Summary: Our recent study found that APOBEC3B is upregulated in the preinvasive stages of non-small cell lung cancer and breast cancer. We suggest that APOBEC3 promotes copy number intratumor heterogeneity prior to invasion, thereby providing a substrate for cancer evolution.
MOLECULAR & CELLULAR ONCOLOGY
(2023)
