A new research perspective was published in Oncotarget's Volume 14 on February 4, 2023, entitled, “The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.”

CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy. 

However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade. 

In this new research perspective, researchers Anqi Shao and David M. Owens from Columbia University Irving Medical Center summarized the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.

“In the future, unbiased genomic- and proteomic-based approaches may help to clarify these issues by identifying tumor-specific mechanisms of CD200 expression regulation across a variety of human cancers that may be leveraged for broader therapeutic benefit.”

DOI: https://doi.org/10.18632/oncotarget.28354 

Correspondence to: David M. Owens - do2112@cumc.columbia.edu 

Keywords: CD200 receptor, oncoimmunology, immunotherapy, tumor microenvironment, immune checkpoint inhibition

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

Immunoregulatory Protein CD200 as Potentially Lucrative Yet Elusive Cancer Therapy Target

A new review paper was published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Crosstalk between triple negative breast cancer and microenvironment.”

Although many advances have been made in the treatment of breast cancer, for triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but effective therapies are currently not available. 

In their new review, researchers Karly Smrekar, Artem Belyakov and Kideok Jin from Albany College of Pharmacy and Health Science discuss recent progress in our understanding of TNBC, advancements in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC.

“Technological advancements such as genomics and epigenomics have provided us with vast insight about the complexity of breast cancer. However, one thing has remained the same, the need for the evaluation of three markers. These three markers; the expression of estrogen, progesterone, and HER2, are all molecular targets for treatment regimens, and are relied on by clinicians [1]. Chemotherapy is the staple treatment for TNBC patients. However, they lack the expression of three key therapeutic markers. The lack of therapeutic markers leads to poorer outcomes in TNBC.”

DOI: https://doi.org/10.18632/oncotarget.28397 

Correspondence to: Kideok Jin - kideok.jin@acphs.edu 

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Keywords - triple negative breast cancer, tumor microenvironment, current therapy

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Crosstalk Between Triple Negative Breast Cancer and Microenvironment

A new research perspective was published in Oncotarget's Volume 14 on April 26, 2023, entitled, “Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism.”

Colon cancer (CRC) is one of the most common malignancies and is a leading cause of cancer-related deaths worldwide. While the tumor microenvironment (TME) supports tumor growth and immune escape through tumor-promoting inflammation, the mechanisms by which the TME promotes CRC are far from being elucidated. Stromal myo-/fibroblasts (MFs) account for up to 30% of lamina propria cells in the normal human colon and their number is dramatically increased in CRC. 

Fibroblasts from cancers, also known as cancer-associated fibroblasts (CAFs), differ from normal colonic MF (N-MFs) and support tumor-promoting inflammation, in part due to increased IL-6 secretion. CAFs are very abundant in the TME and are among the major cells involved in tumor inflammation and progression. In this research perspective, researchers Romain Villéger, Marina Chulkina, Randy C. Mifflin, Don W. Powell, and Irina V. Pinchuk from the Université de Poitiers, Penn State Health Milton S. Hershey Medical Center and The University of Texas Medical Branch highlight recent data obtained regarding IL-6 regulation in colorectal cancer CAFs through vitamin A (retinol) metabolism, discuss current limitations in our understanding of the mechanisms leading to the CAF pro-inflammatory phenotype, and discuss potential approaches to target CAF retinoid metabolism during CRC treatment.

"While the overall mechanisms responsible for the IL-6 increase within the CRC tumor stroma remain to be elucidated, our study highlights the crucial role of stromal vitamin A pathway in IL-6 regulation."

DOI: https://doi.org/10.18632/oncotarget.28399

Correspondence to - Iryna V. Pinchuk - ipinchuk@pennstatehealth.psu.edu

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Keywords - tumor microenvironment, colon cancer, inflammation, fibroblasts, IL-6

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Retinol Disruption and The Role of Vitamin A Metabolism in Colon Cancer

A new research perspective was published in Oncotarget's Volume 14 on May 10, 2023, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.”

Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are highly metastatic cancers with poor survival rates. The tumor microenvironment has been shown to play a critical role in cancer progression and response to therapies. Endothelial cells (ECs) are a key component of the tumor microenvironment and promote cancer cell survival by secreting soluble factors that activate cancer-promoting signaling pathways. 

In this new perspective, researchers Omkar Desai and Rui Wang from Case Western Reserve University and University Hospitals Cleveland Medical Center discuss their studies and others that have identified HER3 as a key mediator of liver EC-induced chemoresistance and cancer cell growth in metastatic CRC and PDAC. 

“In complement to our studies, prior preclinical studies have shown that HER3-targeted therapies with antibodies and inhibitors have been effective in blocking tumor growth in several types of cancers [22, 23], specifically breast cancer [24], head and neck squamous cell carcinoma (HNSCC) [25], PDAC [25], and non-small cell lung cancer (NSCLC) [26]. However, translating the preclinical findings to clinical studies has shown limited impact on patient outcomes.”

In this article, the researchers discuss that HER3-targeted therapies may be effective in treating patients with HER3-expressing CRC and PDAC, and highlight the importance of applying HER3 expression as a predictive biomarker for patient response to HER3-targeted therapies. They also discuss the challenges encountered in past clinical trials of HER3-targeted therapies, including the role of NRG1 gene fusions, alternative HER3 activation mechanisms, and adaptive resistance mechanisms. Finally, the team concludes by suggesting the future directions of HER3-targeted therapies, including novel approaches to overcome chemoresistance and promote cancer cell death.

“In summary, we discovered that the surrounding liver EC microenvironment plays a key role in activating HER3 and promoting cell survival in mCRC and mPDAC, and potentially other types of cancer that metastasize to the liver.”

DOI - https://doi.org/10.18632/oncotarget.28421

Correspondence to - Rui Wang -  rxw517@case.edu

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Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironment

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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HER3: Survival Pathway and Therapeutic Target in Metastatic Colorectal and Pancreatic Cancer

A new editorial paper was published in Oncotarget's Volume 14 on August 10, 2023, entitled, “Inhibition of glutamine metabolism: acting on tumoral cells or on tumor microenvironment?”

Cancer cell growth and survival relies on metabolites and metabolic routes different from those used by healthy cells. Glucose and glutamine (Gln) uptake and consumption is increased by many cancer types in order to support their high growth rate. Besides being metabolized to tricarboxylic acid (TCA) cycle precursors, Gln is necessary also for the generation of nitrogen-containing metabolites, such as nucleotides, glucosamine-6-phosphate or nonessential amino acids. Indeed, nitrogen supply has been widely described as limiting for cell cycle progression. 

As mitochondrial glutaminase (GLS) directs Gln into the TCA cycle, its inhibition has been suggested as a potential strategy for targeting and blocking Gln metabolism in cancer cells. In fact, GLS inhibitors block cancer cell growth in vivo and in vitro. Based on this premise, several clinical studies have been conducted to test if Gln dysregulation increases cancer patients’ survival. So far, these treatments have not been able to induce a great overall benefit for patients due to the ability of tumor cells to alter their metabolism. 

Different authors have described an increase in the oxidative stress after alterations in Gln metabolism in vivo, suggesting the possibility to combine glutamine dysregulation strategies with some other therapies increasing reactive oxidative species to promote cancer cell death. In his new editorial, researcher Raul Peña from Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) discusses a novel mechanism by which Gln, usually concentrated at the tumor periphery, acts as a chemoattractant for cancer-associated fibroblasts (CAFs), enhancing extracellular matrix degradation and facilitating epithelial cancer cell migration and metastasis in vivo. 

“Recently, we described a new action of Gln on cancer-associated fibroblasts (CAFs) in breast cancer. [...] In our study, we determined that mesenchymal-like epithelial breast tumor cells and CAFs present a higher dependence on Gln than tumor epithelial breast cancer cells.”

DOI - https://doi.org/10.18632/oncotarget.28443

Correspondence to - Raúl Peña - rpena@imim.es

Video short - https://www.youtube.com/watch?v=HcI9CpUdbys

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Keywords - cancer, glutamine, tumor microenvironment, fibroblasts, CAF, snail1

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Inhibiting Glutamine Metabolism Impacts Tumor Cells or the Microenvironment?

Dr. Omkar Desai, from the Department of Surgery at Case Western Reserve University and University Hospitals Cleveland Medical Center, describes a research perspective he co-authored with Dr. Rui Wang that was published by Oncotarget in Volume 14, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.”

DOI - https://doi.org/10.18632/oncotarget.28421

Correspondence to - Rui Wang - rxw517@case.edu

Author video - https://www.youtube.com/watch?v=3-02jt7-MW8

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Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironment

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Behind the Study: HER3: A Vital Target in Cancer Treatment

HER3: A Vital Target in Cancer Treatment

BUFFALO, NY- February 28, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures.”

Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. In this new study, researchers Ying Dong, Xiaoqing Wu, Chaojie Xu, Yasir Hameed, Mostafa A. Abdel-Maksoud, Taghreed N. Almanaa, Mohamed H. Kotob, Wahidah H. Al-Qahtani, Ayman M. Mahmoud, William C. Cho, and Chen Li from Shenzhen Second People’s Hospital, China Academy of Chinese Medical Sciences, Peking University, The Islamia University of Bahawalpur, King Saud University, University of Vienna, Manchester Metropolitan University, Queen Elizabeth Hospital, and Free University of Berlin focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. 

“Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers.”

Full press release - https://www.aging-us.com/news-room/Prognostic-Model-Development-and-Molecular-Subtypes-Identification-in-Bladder-Urothelial-Cancer

DOI - https://doi.org/10.18632/aging.205499

Corresponding authors - Yasir Hameed - Yasirhameed2011@gmail.com, William C. Cho - chocs@ha.org.hk, and Chen Li - chen.li@fu-berlin.de

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Keywords - aging, oxidative stress, bladder urothelial cancer, tumor microenvironment, immunotherapy

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Aging (Aging-US)

Prognostic Model Development and Molecular Subtypes Identification in Bladder Urothelial Cancer

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

New tracks tagged #microenvironment