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. Recent studies have revealed that some conventional and targeted therapy strategies can augment the efficacy of immunotherapy even in patients with less immunogenic solid tumors. These strategies provoke immunogenic cell death (ICD) through the ROS-dependent liberation of damage-associated molecular patterns (DAMPs). These DAMPs recognize and bind with Pattern Recognition Receptors (PRRs) on immune cells, activating and maturing defense cells, ultimately leading to a robust antitumor immune response. The present review underscores the pivotal role of redox homeostasis in orchestrating the transition of TME from a cold to a hot phenotype and the ROS-ICD axis in immune response induction. Additionally, it provides up-to-date insights into strategies that leverage ROS generation to induce ICD. The comprehensive analysis aims to develop ROS-based effective cancer immunotherapies for less immunogenic tumors.

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. HER2 modulates transcription factors critical for cancer stem cell properties, further impacting drug resistance. HER2 activity is influenced by HER-family ligands, promoting oncogenic signaling. These features point to HER2 as a targetable driver in GC. This review outlines recent advances in HER2-mediated mechanisms and their upstream and downstream signaling pathways in GC. Additionally, it discusses preclinical research investigation that comprehends trastuzumab-sensitizing phytochemicals, chemotherapeutics, and nanoparticles as adjunct therapies. These developments hold promise for improving outcomes and enhancing the management of HER2-positive GC.

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. This review delves into the potential of neoAgs and CTAs as vaccine candidates, emphasizing diverse strategies and delivery approaches. It also highlights the current status of vaccination modalities undergoing clinical trials in TNBC therapy. A comprehensive understanding of neoAgs, CTAs, vaccination strategies, and innovative delivery methods is crucial for optimizing neoAg-based immunotherapies in clinical practice.

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. They manipulate the body's cellular functions to produce antigens, elicit immune responses, and suppress tumors by overcoming limitations associated with specific histocompatibility leukocyte antigen molecules. However, successfully delivering mRNA into target cells destroys a crucial challenge. Viral and nonviral vectors (lipid nanoparticles and cationic liposomes) have shown great capacity in protecting mRNA from deterioration and assisting in cellular uptake. Cell-penetrating peptides, hydrogels, polymer-based nanoparticles, and dendrimers have been investigated to increase the delivery efficacy and immunogenicity of mRNA. This comprehensive review explores the landscape of mRNA vaccines and their delivery platforms for cancer, addressing design considerations, diverse delivery strategies, and recent advancements. Overall, this review contributes to the progress of mRNA vaccines as an innovative strategy for effective cancer treatment.

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.

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. Resveratrol is the natural polyphenolic stilbene in vegetables and fruits like grapes and apples. It inhibits CRC progression via targeting dysregulated cancer-promoting pathways, including PI3K/Akt/Kras, targeting transcription factors like NF-κB and STAT3, and an immunosuppressive tumor microenvironment. In addition, combination therapies for cancer include resveratrol as an adjuvant to decrease multidrug resistance that develops in CRC cells. The current review discusses the biology of resveratrol and explores different mechanisms of action of resveratrol in inhibiting CRC progression. Further, the detrimental role of resveratrol on the immunosuppressive tumor microenvironment of CRC has been discussed. This review illustrates clinical trials on resveratrol in different cancers, including resveratrol analogs, and their efficiency in promoting CRC inhibition.