Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a significant global health burden, with increasing incidence rates and limited treatment options. Immunotherapy has become a promising approach due to its ability to affect the immune microenvironment and promote antitumor responses. The immune microenvironment performs an essential role in both the progression and the development of HCC, with different characteristics based on specific immune cells and etiological factors. Immune checkpoint inhibitors, including programmed death-1/programmed death-ligand 1 inhibitors (pembrolizumab, nivolumab, and durvalumab) and cytotoxic T lymphocyte antigen-4 inhibitors (tremelimumab and ipilimumab), have the potential to treat advanced HCC and overcome adverse effects, such as liver failure and chemoresistance. Phase II and phase III clinical trials highlight the efficacy of pembrolizumab and nivolumab, respectively, in advanced HCC patients, as demonstrated by their positive effects on overall survival and progression-free survival. Tremelimumab has exhibited modest response rates, though it does possess antiviral activity. Thus, it is still being investigated in ongoing clinical trials. Combination therapies with multiple drugs have demonstrated potential benefits in terms of survival and tumor response rates, improving patient outcomes compared to monotherapy, especially for advanced-stage HCC. This review addresses the clinical trials of immunotherapies for early-, intermediate-, and advanced-stage HCC. Additionally, it highlights how combination therapy can significantly enhance overall survival, progression-free survival, and objective response rate in advanced-stage HCC, where treatment options are limited.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo–YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies—either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)—can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment.

Hepatocellular carcinoma (HCC) is the most common liver cancer, with poor survival rates in advanced stages due to late diagnosis, tumor heterogeneity, and therapy resistance. The tumor microenvironment (TME) in HCC has a crucial role in tumor progression, characterized by a complex interaction of immune cells, stromal components, and immunosuppressive signaling pathways. Chronic inflammation driven by viral infections, metabolic dysfunction, and alcohol consumption triggers an immunosuppressive TME, promoting immune evasion and tumor growth. Immune cell populations, such as myeloid-derived suppressor cells, regulatory T cells, and tumor-associated macrophages, contribute to immunosuppression, while cytotoxic T lymphocytes and natural killer cells exert anti-tumor effects. Recent advances in immunotherapy, mainly immune checkpoint inhibitors (ICIs) targeting programmed death-ligand 1 and programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4, have revolutionized HCC treatment, though response rates remain limited. Combined therapies using tyrosine kinase inhibitors, anti-angiogenic agents, and ICIs improve patient outcomes. This review discusses the immunological mechanisms contributing to HCC progression, the role of immune cell subsets in tumor evasion, and therapeutic interventions, from conventional treatments to advanced immunotherapies. Ongoing clinical trials, barriers to effective treatment, and future directions to enhance HCC management and patient survival will also be overviewed.

Hepatocellular carcinoma (HCC) is the deadliest emergent health issue around the globe. The stronger oncogenic effect, proteins, and weakened immune response are precisely linked with a significant prospect of developing HCC. Several conventional systemic therapies, antiangiogenic therapy, and immunotherapy techniques have significantly improved the outcomes for early-, intermediate-, and advanced-stage HCC patients, giving new hope for effective HCC management and prolonged survival rates. Innovative therapeutic approaches beyond conventional treatments have altered the landscape of managing HCC, particularly focusing on targeted therapies and immunotherapies. The advancement in HCC treatment suggested by the Food and Drug Administration is multidimensional treatment options, including multikinase inhibitors (sorafenib, lenvatinib, regorafenib, ramucirumab, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, durvalumab, tremelimumab, ipilimumab, and nivolumab), in monotherapy and in combination therapy to increase life expectancy of HCC patients. This review highlights the efficacy of multikinase inhibitors and immune checkpoint inhibitors in monotherapy and combination therapy through the analysis of phase II, and III clinical trials, targeting the key molecular pathways involved in cellular signaling and immune response for the prospective treatment of advanced and unresectable HCC and discusses the upcoming combinations of immune checkpoint inhibitors-tyrosine kinase inhibitors and immune checkpoint inhibitors-vascular endothelial growth factor inhibitors. Finally, the hidden challenges with pharmacological therapy for HCC, feasible solutions for the future, and implications of possible presumptions to develop drugs for HCC treatment are reported.

Plants, as sessile organisms, rely on sophisticated gene regulatory networks (GRNs) to adapt to dynamic environmental conditions. Among the central components of these networks are the interconnected pathways of light signaling and circadian rhythms, which together optimize growth, development, and stress resilience. While light and circadian pathways have been extensively investigated independently, their integrative coordination in mediating climate change adaptation responses remains a critical knowledge gap. Light perception via photoreceptors initiates transcriptional reprogramming, while the circadian clock generates endogenous rhythms that anticipate daily and seasonal changes. This review explores the molecular integration of light and circadian signaling, emphasizing how their crosstalk fine-tunes GRNs to balance resource allocation, photomorphogenesis, and stress adaptation. We highlight recent advances in systems biology tools, e.g., single-cell omics, CRISPR screens that unravel spatiotemporal regulation of shared hubs like phytochrome-interacting factors (PIFs), ELONGATED HYPOCOTYL 5 (HY5), and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1). Here, we synthesize mechanistic insights across model and crop species to bridge fundamental molecular crosstalk with actionable strategies for enhancing cropresilience. Moreover, we have tried to discuss agricultural implications in engineering light–clock interactions for the enhancement in crop productivity under climate change scenarios. Through synthesizing mechanistic insights and translational applications, this work will help underscore the potential for manipulating light–circadian networks to promote sustainability in agriculture.

Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, with a rising global incidence and a high mortality rate. Chronic infections with hepatitis viruses, along with risk factors such as cirrhosis, metabolic dysfunction-associated steatohepatitis, and metabolic disorders, significantly contribute to HCC development. Systemic inflammation plays a key role in HCC pathogenesis, with inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) emerging as significant prognostic indicators. Elevated NLR and PLR are associated with poor overall survival and progression-free survival in HCC patients, reflecting an imbalance in the immune response and tumor microenvironment (TME). Neutrophils and platelets contribute to tumor progression by promoting inflammation, angiogenesis, and immune evasion, while lymphocytes, particularly CD8+ T-cells, play essential roles in antitumor immunity. High levels of NLR and PLR are linked to adverse clinical outcomes, including shorter survival times and higher recurrence rates. These ratios provide valuable prognostic information and are increasingly utilized in clinical settings to guide treatment decisions. This review focuses on the roles of inflammatory markers, particularly NLR and PLR, in HCC progression and prognosis, examining their effects on the TME and their potential for improving diagnostic and prognostic strategies. The use of these inflammatory markers and emerging technologies holds promise for enhancing early detection and personalized treatment strategies, ultimately improving patient outcomes in HCC.