Immunoglobulin-binding protein and Toll-like receptors in immune landscape of breast cancer.

Breast cancer (BC) is a complex disease exhibiting significant heterogeneity and encompassing various molecular subtypes. Among these, triple-negative breast cancer (TNBC) stands out as one of the most challenging types, characterized by its aggressive nature and poor prognosis. This review embarks on a comprehensive exploration of the immune landscape of BC, with a primary focus on the functional and structural characterization of immunoglobulin-binding protein (BiP) and its pivotal role in regulating the unfolded response (UPR) pathway of proteins.

Reactive oxygen species of tumor microenvironment: Harnessing for immunogenic cell death.

The tumor microenvironment (TME) is a dynamic and complex system that undergoes continuous changes in its network architecture, notably affecting redox homeostasis. These alterations collectively shape a diverse ecosystem actively supporting tumor progression by influencing the cellular and molecular components of the TME. Despite the remarkable clinical advancements in cancer immunotherapy, its spectrum of clinical utility is limited by the altered TME and inadequate tumor immunogenicity.

Combination of dual JAK/HDAC inhibitor with regorafenib synergistically reduces tumor growth, metastasis, and regorafenib-induced toxicity in colorectal cancer.

Background: Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models.

CD44/PD-L1-mediated networks in drug resistance and immune evasion of breast cancer stem cells: Promising targets of natural compounds.

Cancer stem cells (CSCs) significantly interfere with immunotherapy, leading to challenges such as low response rates and acquired resistance. PD-L1 expression is associated with the CSC population's overexpression of CD44. Mounting evidence suggests that the breast cancer stem cell (BCSC) marker CD44 and the immune checkpoint PD-L1 contribute to treatment failure through their networks.

HER-2 positive gastric cancer: Current targeted treatments.

Gastric cancer (GC) is highly metastatic and characterized by HER2 amplification. Aberrant HER2 expression drives metastasis, therapy resistance, and tumor recurrence. HER2 amplification contributes to drug resistance by upregulating DNA repair enzymes and drug afflux proteins, reducing drug efficacy.

Small molecular inhibitors: Therapeutic strategies for pancreatic cancer.

Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively.

Neoantigens and cancer-testis antigens as promising vaccine candidates for triple-negative breast cancer: Delivery strategies and clinical trials.

Immunotherapy is gaining prominence as a promising strategy for treating triple-negative breast cancer (TNBC). Neoantigens (neoAgs) and cancer-testis antigens (CTAs) are tumor-specific targets originating from somatic mutations and epigenetic changes in cancer cells. These antigens hold great promise for personalized cancer vaccines, as supported by preclinical and early clinical evidence in TNBC.

A Novel Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth in Mouse Models of GI Cancer.

Unlabelled: Here, we describe a novel pan-RAS inhibitor, ADT-007, that potently inhibited the growth of RAS mutant cancer cells irrespective of the RAS mutation or isozyme. RAS cancer cells with GTP-activated RAS from upstream mutations were equally sensitive. Conversely, RAS cancer cells harboring downstream BRAF mutations and normal cells were essentially insensitive to ADT-007.

Breaking the stromal barrier in pancreatic cancer: Advances and challenges.

Pancreatic cancer (PC) remains a leading cause of mortality worldwide due to the absence of early detection methods and the low success rates of traditional therapeutic strategies. Drug resistance in PC is driven by its desmoplastic stroma, which creates a barrier that shields cancer niches and prevents the penetration of drugs. The PC stroma comprises heterogeneous cellular populations and non-cellular components involved in aberrant ECM deposition, immunosuppression, and drug resistance.

Unleashing the Power of Yes-Associated Protein in Ferroptosis and Drug Resistance in Breast Cancer, with a Special Focus on Therapeutic Strategies.

The YAP protein is a critical oncogenic mediator within the Hippo signaling pathway and has been implicated in various cancer types. In breast cancer, it frequently becomes activated, thereby contributing to developing drug-resistance mechanisms. Recent studies have underscored the intricate interplay between YAP and ferroptosis within the breast tumor microenvironment.

Obesity associated pancreatic ductal adenocarcinoma: Therapeutic challenges.

Obesity is a prominent health issue worldwide and directly impacts pancreatic health, with obese individuals exhibiting a significant risk for increasing pancreatic ductal adenocarcinoma (PDAC). Several factors potentially explain the increased risk for the development of PDAC, including obesity-induced chronic inflammation within and outside of the pancreas, development of insulin resistance and metabolic dysfunction, promotion of immune suppression within the pancreas during inflammation, pre- and malignant stages, variations in hormones levels (adiponectin, ghrelin, and leptin) produced from the adipose tissue, and acquisition of somatic mutations in tumor once- and suppressor proteins critical for pancreatic tumorigenesis. In this manuscript, we will explore the broad impact of these obesity-induced risk factors on the development and progression of PDAC, focusing on changes within the tumor microenvironment (TME) as they pertain to prevention, current therapeutic strategies, and future directions for targeting obesity management as they relate to the prevention of pancreatic tumorigenesis.

mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer.

mRNA vaccines have evolved as promising cancer therapies. These vaccines can encode tumor-allied antigens, thus enabling personalized treatment approaches. They can also target cancer-specific mutations and overcome immune evasion mechanisms.

Resveratrol: biology, metabolism, and detrimental role on the tumor microenvironment of colorectal cancer.

A substantial increase in colorectal cancer (CRC)-associated fatalities can be attributed to tumor recurrence and multidrug resistance. Traditional treatment options, including radio- and chemotherapy, also exhibit adverse side effects. Ancient treatment strategies that include phytochemicals like resveratrol are now widely encouraged as an alternative therapeutic option.

Colorectal cancer: Genetic alterations, novel biomarkers, current therapeutic strategies and clinical trials.

Colorectal cancer (CRC) is the third most commonly detected cancer with a serious global health issue. The rates for incidence and mortality for CRC are alarming, especially since the prognosis is abysmal when the CRC is diagnosed at an advanced or metastatic stage. Both type of (modifiable/ non-modifiable) types of risk factors are established for CRC.

Gemcitabine effects on tumor microenvironment of pancreatic ductal adenocarcinoma: Special focus on resistance mechanisms and metronomic therapies.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest malignancies, with dismal survival rates and extremely prevalent chemoresistance. Gemcitabine is one of the primary treatments used in treating PDACs, but its benefits are limited due to chemoresistance, which could be attributed to interactions between the tumor microenvironment (TME) and intracellular processes. In preclinical models, certain schedules of administration of gemcitabine modulate the TME in a manner that does not promote resistance.

Targeting the metabolism and immune system in pancreatic ductal adenocarcinoma: Insights and future directions.

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), presents a challenging landscape due to its complex nature and the highly immunosuppressive tumor microenvironment (TME). This immunosuppression severely limits the effectiveness of immune-based therapies. Studies have revealed the critical role of immunometabolism in shaping the TME and influencing PDAC progression.

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer.

HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms.

Understanding the molecular mechanisms that regulate pancreatic cancer stem cell formation, stemness and chemoresistance: A brief overview.

Pancreatic cancer is one of the most aggressive cancers worldwide due to the resistances to conventional therapies and early metastasis. Recent research has shown that cancer stem cell populations modulate invasiveness, recurrence, and drug resistance in various cancers, including pancreatic cancer. Pancreatic cancer stem cells (PaCSCs) are characterized by their high plasticity and self-renewal capacities that endow them with unique metabolic, metastatic, and chemoresistant properties.

Mitochondrial-targeted nanoparticles: Delivery and therapeutic agents in cancer.

Mitochondria are the powerhouses of cells and modulate the essential metabolic functions required for cellular survival. Various mitochondrial pathways, such as oxidative phosphorylation or production of reactive oxygen species (ROS) are dysregulated during cancer growth and development, rendering them attractive targets against cancer. Thus, the delivery of antitumor agents to mitochondria has emerged as a potential approach for treating cancer.

Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity.

Pancreatic neuroendocrine tumors (pNETs) are extremely diverse and highly vascularized neoplasms that arise from endocrine cells in the pancreas. The pNETs harbor a subpopulation of stem cell-like malignant cells, known as cancer stem cells (CSCs), which contribute to intratumoral heterogeneity and promote tumor maintenance and recurrence. In this study, we demonstrate that CSCs in human pNETs co-express protein kinase PKD1 and CD44.

Pyroptosis-based nanotherapeutics: Possible mechanisms for cancer treatment.

Pyroptosis represents an inflammatory cell death form induced by inflammasomes and performed by gasdermins. It is characterized by swelling, pore formation, release of cellular content and the activation of innate immunity leading to inflammation. Hence, pyroptosis contributes to inflammatory conditions like cancer and has emerged as a promising immuno-strategy for treating cancer.

Fibroblast heterogeneity in pancreatic ductal adenocarcinoma: Perspectives in immunotherapy.

Cancer-associated fibroblasts (CAFs), the key component in pancreatic tumor microenvironment (TME), originate from many sources and are naturally heterogeneous in phenotype and function. Numerous studies have identified their crucial role in promoting tumorigenesis through many routes including fostering cancer proliferation, angiogenesis, invasion, and metastasis. Conversely, research also indicates that subsets of CAFs express anti-tumor activity.

Pleiotropic roles of evolutionarily conserved signaling intermediate in toll pathway (ECSIT) in pathophysiology.

The evolutionarily conserved signaling intermediate in toll pathway (ECSIT) is a cytosolic adaptor protein associated with the toll-like receptor pathway. It has a distinct N-terminal mitochondrial targeting sequence, pentatricopeptide repeat motif, and a C-terminal pleckstrin homology domain. ECSIT regulates many biological processes like embryonic development, inflammation, cardiac function, and assembly of mitochondrial complex I.

Nanoparticles mediated tumor microenvironment modulation: current advances and applications.

The tumor microenvironment (TME) plays a key role in cancer development and emergence of drug resistance. TME modulation has recently garnered attention as a potential approach for reprogramming the TME and resensitizing resistant neoplastic niches to existing cancer therapies such as immunotherapy or chemotherapy. Nano-based solutions have important advantages over traditional platform and can be specifically targeted and delivered to desired sites.