Tumor secretome shapes the immune landscape during cancer progression.

The focus of cancer immunotherapy has traditionally been on immune cells and tumor cells themselves, often overlooking the tumor secretome. This review provides a comprehensive overview of the intricate relationship between tumor cells and the immune response in cancer progression. It highlights the pivotal role of the tumor secretome - a diverse set of molecules secreted by tumor cells - in significantly influencing immune modulation, promoting immunosuppression, and facilitating tumor survival.

Exploring the impact of GSTM1 as a novel molecular determinant of survival in head and neck cancer patients of African descent.

Background: Blacks/African American (BAA) patients diagnosed with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes than White patients. However, the mechanisms underlying racial disparities in HNSCC have not been thoroughly characterized.

Methods: Data on gene expression, copy number variants (CNVs), gene mutations, and methylation were obtained from 6 head and neck cancer datasets.

Cell death shapes cancer immunity: spotlighting PANoptosis.

PANoptosis represents a novel type of programmed cell death (PCD) with distinctive features that incorporate elements of pyroptosis, apoptosis, and necroptosis. PANoptosis is governed by a newly discovered cytoplasmic multimeric protein complex known as the PANoptosome. Unlike each of these PCD types individually, PANoptosis is still in the early stages of research and warrants further exploration of its specific regulatory mechanisms and primary targets.

Cancer metabolism and carcinogenesis.

Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing them to adapt to different microenvironments and therapeutic interventions. This refers to metabolic heterogeneity, in which different cell populations use different metabolic pathways to sustain their survival and proliferation and impact their response to conventional cancer therapies.

Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer.

Unlabelled: Radiotherapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet radioresistance remains a major barrier to therapeutic efficacy. A better understanding of the predominant pathways determining radiotherapy response could help develop mechanism-informed therapies to improve cancer management. Here we report that radioresistant HNSCC cells exhibit increased tumor aggressiveness.

Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States.

Background: Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.

ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.

Background: Targeting mitochondrial oncoproteins presents a new concept in the development of effective cancer therapeutics. ATAD3A is a nuclear-encoded mitochondrial enzyme contributing to mitochondrial dynamics, cholesterol metabolism, and signal transduction. However, its impact and underlying regulatory mechanisms in cancers remain ill-defined.

Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.

Background: Alterations in metabolism are one of the emerging hallmarks of cancer cells and targeting dysregulated cancer metabolism provides a new approach to developing more selective therapeutics. However, insufficient blockade critical metabolic dependencies of cancer allows the development of metabolic bypasses, thus limiting therapeutic benefits.

Methods: A series of head and neck squamous cell carcinoma (HNSCC) cell lines and animal models were used to determine the efficacy of CPI-613 and CB-839 when given alone or in combination.

Evaluating the Anticancer Activity of Natural Products Using a Novel 3D Culture Model.

Natural products, particularly as anticancer agents, continue to provide prototypes for pharmacologically active compounds. Compared with traditional two-dimensional (2D) approaches, 3D cell cultures have shown a clear role in drug discovery and development as they more closely resemble in vivo cell environments and come closer to capturing the in vivo functions of organs and tissues. The growing interest in using more physiological in vitro cancer models has driven the adoption of 3D cell cultures in evaluating anticancer activities of natural products.

PGK1 : An Essential Player in Modulating Tumor Metabolism.

Phosphoglycerate kinase 1 (PGK1) is the first enzyme in glycolysis to generate a molecule of ATP in the conversion of 1,3-bisphosphoglycerate (1,3-BPG) to 3-phosphoglycerate (3-PG). In addition to the role of glycolysis, PGK-1 acts as a polymerase alpha cofactor protein, with effects on the tricarboxylic acid cycle, DNA replication and repair. Posttranslational modifications such as methylation, phosphorylation, and acetylation have been seen to activate PGK1 in cancer.

The New Frontier of Three-Dimensional Culture Models to Scale-Up Cancer Research.

In vitro cancer research models require the utmost accuracy and precision to effectively investigate physiological pathways and mechanisms, as well as test the therapeutic efficacy of anticancer drugs. Although two-dimensional (2D) cell culture models have been the traditional hallmark of cancer research, increasing evidence suggests 2D tumor models cannot accurately recapitulate complex aspects of tumor cells and drug responses. Three-dimensional (3D) cell cultures, however, are more physiologically relevant in oncology as they model the cancer network and microenvironment better, allowing for development and assessment of natural products and other anticancer drugs.

SHOX2 cooperates with STAT3 to promote breast cancer metastasis through the transcriptional activation of WASF3.

Background: Metastasis is most often the root cause of cancer-related death. Human short stature homeobox 2 (SHOX2), a homeodomain transcription factor, is a novel inducer of epithelial-to-mesenchymal transition in breast cancer cells, though its exact role and underlying mechanisms in metastasis are not well understood.

Methods: TCGA analysis was performed to identify the clinical relevance of SHOX2 in breast cancer.

Multifaceted Roles of Long Non-coding RNAs in Head and Neck Cancer.

The majority of RNA transcripts are non-coding RNA (ncRNA) transcripts with lengths exceeding 200 nucleotides that are not translated into protein. Unlike microRNAs (miRNAs), long ncRNAs (lncRNAs) are not confined to a single mechanism of action but have a large and diverse role in biological processes as they can function as transcription regulators, decoys, scaffolds, and enhancer RNAs. Currently, many lncRNA molecules are under investigation for their role in tumorigenesis, metastasis, and prognosis in different types of cancer.

FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis.

Background: There is no consensus about the effective dosages of melatonin in cancer management, thus, it is imperative to fully understand the dose-dependent responsiveness of cancer cells to melatonin and the underlying mechanisms.

Methods: Head and neck squamous cell carcinoma (HNSCC) cells with or without melatonin treatment were used as a research platform. Gene depletion was achieved by short hairpin RNA, small interfering RNA, and CRISPR/Cas9.

Unveiling Tumor Microenvironment Interactions Using Zebrafish Models.

The tumor microenvironment (TME) is a rich and active arena that is strategically evolved overtime by tumors to promote their survival and dissemination. Over the years, attention has been focused to characterize and identify the tumor-supporting roles and subsequent targeting potentials of TME components. Nevertheless, recapitulating the human TME has proved inherently challenging, leaving much to be explored.

PI3K Isoform-Selective Inhibitors in Cancer.

PI3K inhibitors are a common area of research in finding a successful treatment of cancer. The PI3K pathway is important for cell growth, apoptosis, cell metabolism, cell survival, and a multitude of other functions. There are multiple isoforms of PI3K that can be broken down into three categories: class I, II, and III.

Targeting ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Cancer.

The control of crosstalk between autophagy and apoptosis in tumor cells can remove a critical barrier to comprehensive and efficacious treatment for cancer. Reactive oxygen species (ROS), by-products of redox homeostasis, are critical for regulating the balance between autophagy and apoptosis in cancer cells upon different drug treatments and gene modifications. The mechanisms and consequences involved in ROS-mediated crosstalk between apoptosis and autophagy are extremely complex in cancer cells.

Visualizing and Evaluating Cancer Cell Growth and Invasion by a Novel 3D Culture System.

With the development of new materials and technologies, it is possible to access gene function and drug metabolism using a three-dimensional (3D) cell culture system, which is more suitable for mimicking the in vivo microenvironment of cultured tumor cells ex vivo. SeedEZ is a novel and versatile tool that allows culturing of different types of cells with user convenience and in a desired sequence. This system provides a bridge between traditional 2D culture and animal experiments.

ATAD3A on the Path to Cancer.

The ATPase family AAA-domain containing protein 3A (ATAD3A), a nuclear-encoded mitochondrial enzyme, is involved in diverse cellular processes, including mitochondrial dynamics, cell death and cholesterol metabolism. Overexpression and/or mutation of the ATAD3A gene have been observed in different types of cancer, associated with cancer development and progression. The dysregulated ATAD3A acts as a broker of a mitochondria-endoplasmic reticulum connection in cancer cells, and inhibition of this enzyme leads to tumor repression and enhanced sensitivity to chemotherapy and radiation.

PFKP Signaling at a Glance: An Emerging Mediator of Cancer Cell Metabolism.

Phosphofructokinase-1 (PFK-1), a rate-determining enzyme of glycolysis, is an allosteric enzyme that regulates the oxidation of glucose in cellular respiration. Glycolysis phosphofructokinase platelet (PFKP) is the platelet isoform and works as an important mediator of cell metabolism. Considering that PFKP is a crucial player in many steps of cancer initiation and metastasis, we reviewed the specificities and complexities of PFKP and its biological roles in human diseases, especially malignant tumors.

Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.

Background: Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized.

Methods: Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference.

Histone deacetylase inhibitors suppress aggressiveness of head and neck squamous cell carcinoma via histone acetylation-independent blockade of the EGFR-Arf1 axis.

Background: A promising arsenal of histone deacetylase (HDAC)-targeted treatment has emerged in the past decade, as the abnormal targeting or retention of HDACs to DNA regulatory regions often occurs in many cancers. Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies worldwide associated with poor overall survival in late-stage patients. HDAC inhibitors have great potential to treat this devastating disease; however, few has been studied regarding the beneficial role of HDAC inhibition in anti-HNSCC therapy and the underlying molecular mechanisms remain elusive.

FGF19 amplification reveals an oncogenic dependency upon autocrine FGF19/FGFR4 signaling in head and neck squamous cell carcinoma.

The fibroblast growth factor 19 gene FGF19 has previously been reported to be amplified in several cancer types and encodes for a key autocrine signaler known to promote tumorigenic growth. Thus, it is imperative to understand which cancers are oncogenically addicted to FGF19 amplification as well as the role it serves in these cancer types. We report for the first time high FGF19 amplification in head and neck squamous cell carcinomas (HNSCC), which is associated with increased autocrine secretion of FGF19 and poor patient outcome in HNSCC.