Immunotherapy and Radiation Therapy Combinatorial Approaches in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a prevalent and often fatal liver cancer, presents significant treatment challenges, especially in its advanced stages. This article delves into the promising approach of combining immunotherapy, particularly immune checkpoint inhibitors, with radiation therapy, a cornerstone of HCC management. Our review synthesizes current preclinical and clinical research, highlighting the potential synergistic effects of this combinational treatment. Emerging evidence suggests that this synergy enhances tumor control and improves patient survival rates. The combination leverages the localized, tumor-targeting ability of radiation therapy and the systemic, immune-boosting effects of immunotherapy, potentially overcoming the limitations inherent in each treatment modality when used separately. This integrative approach is especially promising in addressing the complex tumor microenvironment of HCC. However, the treatment landscape is nuanced, with challenges such as patient-specific response variability and potential resistance to therapies. Future research directions should focus on refining these combination strategies, tailoring them to individual patient profiles, and understanding the underlying mechanisms that govern the interaction between immunotherapy and radiation therapy. Such advancements could significantly improve HCC management, setting new standards for patient care and treatment efficacy.

Targeting Angiogenesis Alone and in Combination with Immune Checkpoint Inhibitors in Advanced Gastroesophageal Malignancies.

PURPOSE OF REVIEW: This review critically examines the latest approaches in treating advanced gastroesophageal malignancies. It emphasizes the significance of angiogenesis as a therapeutic target and discusses the potential synergy of combining angiogenesis inhibitors with immune checkpoint inhibitors (ICIs) to enhance treatment efficacy. RECENT FINDINGS: Emerging evidence from clinical trials, such as the INTEGRATE IIa trial with regorafenib and studies involving apatinib and sunitinib, underscores the efficacy of targeting the VEGFR pathway. These studies indicate substantial benefits in progression-free survival (PFS) and overall survival (OS) in patients with advanced stages of the disease who have limited treatment options. Additionally, the recent introduction of combination therapies involving ICIs has shown an increased response rate, suggesting a promising direction for future treatment protocols. The landscape of treatment for gastroesophageal malignancies is rapidly evolving. Research is now pivoting from conventional chemotherapy to a more nuanced approach that includes targeted therapy and immunotherapy.

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches.

SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple human cancers and is considered a promising therapeutic target for treating these malignancies. The PTPN11 gene and functions encode SHP2 as a critical signal transduction regulator that interacts with key signaling molecules in both the RAS/ERK and PD-1/PD-L1 pathways; SHP2 is also implicated in T-cell signaling. SHP2 may be inhibited by molecules that cause allosteric (bind to sites other than the active site and attenuate activation) or orthosteric (bind to the active site and stop activation) inhibition or via potent SHP2 degraders. These inhibitors have anti-proliferative effects in cancer cells and suppress tumor growth in preclinical models. In addition, several SHP2 inhibitors are currently in clinical trials for cancer treatment. This review aims to provide an overview of the current research on SHP2 inhibitors, including their mechanism of action, structure-activity relationships, and clinical development, focusing on immune modulation effects and novel therapeutic strategies in the immune-oncology field.

SLAM Modification as an Immune-Modulatory Therapeutic Approach in Cancer.

In the field of oncology, the Signaling Lymphocyte Activation Molecule (SLAM) family is emerging as pivotal in modulating immune responses within tumor environments. The SLAM family comprises nine receptors, mainly found on immune cell surfaces. These receptors play complex roles in the interaction between cancer and the host immune system. Research suggests SLAM's role in both enhancing and dampening tumor-immune responses, influencing the progression and treatment outcomes of various cancers. As immunotherapy advances, resistance remains an issue. The nuanced roles of the SLAM family might provide answers. With the rise in technologies like single-cell RNA sequencing and advanced imaging, there is potential for precise SLAM-targeted treatments. This review stresses patient safety, the importance of thorough clinical trials, and the potential of SLAM-focused therapies to transform cancer care. In summary, SLAM's role in oncology signals a new direction for more tailored and adaptable cancer treatments.

Anti-Inflammatory and Immune Properties of Polyunsaturated Fatty Acids (PUFAs) and Their Impact on Colorectal Cancer (CRC) Prevention and Treatment.

Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) has become an area of interest given their potential role in modulating inflammation, particularly in the pro-carcinogenic inflammatory environment of the colon. This work reviews the main types of PUFAs, their characteristics, structure, and physiologic role. We then highlight their potential role in preventing CRC, their signaling function vis-à-vis tumorigenic signaling, and their subsequent potential role in modulating response to different treatment modalities. We review pre-clinical and clinical data and discuss their potential use as adjunct therapies to currently existing treatment modalities. Given our understanding of PUFAs' immune and inflammation modulatory effects, we explore the possible combination of PUFAs with immune checkpoint inhibitors and other targeted therapies.

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

The Crosstalk between Microbiome and Immunotherapeutics: Myth or Reality.

The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor's sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the factors regulating this interaction.