The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, especially in macrophage differentiation and function. This review summarizes the key findings regarding KLF4 in normal blood cells and leukemia.

Accumulating evidence suggests that the progression of hepatocellular carcinoma (HCC) is intricately associated with dynamic alterations in microbiota composition. Disruption of gut microbial homeostasis enables pathogenic gut bacteria to translocate to the liver via the gut-liver axis, where they modulate the tumor microenvironment to promote HCC development. Also, they are associated with anti-tumor immune responses. Studies have confirmed that the microbiota exhibits potential as a biomarker for predicting immunotherapy responses, and its can improve clinical efficacy in the treatment of HCC.This review systematically evaluates current evidence elucidating the regulatory mechanisms by which the microbiota governs the progression of HCC, and explores its synergistic interactions with therapeutic strategies for HCC.

Glomus tumors (GTs) are painful and typically benign neoplasms found in the subungual region of the fingertips. However, the occurrence of multiple GT within nerve fascicles in the scapular region is rare.

The leucine-rich pentatricopeptide repeat-containing (LRPPRC) protein, a member of the pentatricopeptide repeat (PPR) family, is a mitochondria-associated protein that regulates various biological processes, including cell cycle progression and mitochondrial gene translation. LRPPRC has also been identified as an important causative gene in several mitochondrial diseases. N6-methyladenosine (m6A) is the most prevalent and extensive modification of mRNA in eukaryotes, playing a significant role in cellular proliferation, differentiation, and oncogenesis. As an m6A regulator, LRPPRC has been shown to play an important role in the development of various human metabolic diseases and malignant tumors. This review mainly focuses on summarizing the biological roles of LRPPRC in a variety of human malignant tumors, emphasizing the molecular mechanisms LRPPRC is involved in and its potential impact on tumor prognosis.

Ovarian cancer is the most lethal gynecologic malignancy, driven by extensive genetic heterogeneity, clonal evolution, and resistance to therapy. Despite advances in treatment, recurrence remains common, highlighting the urgent need for novel therapeutic strategies. Neutrophil extracellular traps (NETs)-web-like DNA-protein complexes released during NETosis-have recently emerged as key facilitators of tumor progression across multiple cancers. However, their role in ovarian cancer remains underexplored. NETs contribute to metastasis, angiogenesis, immune evasion, and chemoresistance, creating a pro-tumorigenic microenvironment. This review identifies critical knowledge gaps in NET-mediated mechanisms in ovarian cancer and introduces, for the first time in this context, the concept of neutrophil hitchhiking, whereby circulating tumor cells exploit neutrophils to enhance metastatic dissemination. We examine molecular pathways driving NETosis and their influence on the tumor microenvironment, highlighting how NET-targeted therapies-including NETosis inhibitors and immune modulators-offer promising avenues to suppress metastasis, restore immune surveillance, and improve treatment outcomes. By illuminating this underexplored axis of neutrophil-tumor interaction, we aim to stimulate research and therapeutic development that could transform ovarian cancer management.

Chromatin modifiers, owing to their enzymatic activities and frequent overexpression or hyperactivation in cancer, have emerged as promising therapeutic targets. Among these, the nuclear receptor-binding SET domain (NSD) family of proteins catalyzes lysine methylation-a key histone post-translational modification that is implicated in diverse biological processes, primarily through the regulation of transcription. Previous studies have demonstrated that NSD proteins are often overexpressed, mutated, or involved in chromosomal translocations in both hematologic malignancies and solid tumors, thereby regulating tumor initiation and progression. Motivated by these insights, a range of NSD-targeting agents, including targeted protein degraders such as proteolysis-targeting chimeras (PROTACs), have been developed and have exhibited notable anti-cancer activities. In this review, we provide an overview of the NSD family of protein, highlighting their roles in regulating anti-tumor immunity and their implications for immunotherapy response and resistance. We further assess the current landscape of NSD-targeted protein degrader-based therapeutics and their potential utility as anti-cancer agents.

Non-small cell lung cancer (NSCLC) is among one of the most common and deadliest malignancies worldwide. With this new era of precision medicine, oncogenic driver genes and immunotherapy have changed the way we classify and treat this disease. Among these genes, the Kirsten rat sarcoma virus (KRAS) gene is the most mutated in NSCLC and has been the focus of numerous clinical trials for targeted therapy over the past few years. Here, we present an in-depth literature review of past, present, and future KRAS mutated NSCLC treatment with KRAS inhibitor monotherapy and combinatorial approaches including immunotherapy. The molecular biology behind KRAS targeted therapy is discussed while highlighting the difficulties of KRAS inhibitor treatment, including resistance, and the next steps needed to overcome them.

The recent discovery of meningeal lymphatic vessels (MLVs) has revolutionized our understanding of immune regulation within the central nervous system (CNS), overturning the long-standing view of the brain as an immune-privileged organ. Glioblastoma (GBM), the most aggressive primary brain tumor, remains therapeutically intractable due to its highly immunosuppressive microenvironment and poor response to conventional and immune-based therapies. Emerging evidence suggests that MLVs play a crucial role in CNS immune surveillance, cerebrospinal fluid drainage, and solute clearance, all of which are directly linked to GBM pathophysiology. This review is motivated by the urgent need to explore novel therapeutic strategies that address GBM's immune escape and therapeutic resistance. We comprehensively analyze the bidirectional interactions between MLVs and GBM, including their role in antigen transport, T cell activation, and tumor dissemination. Furthermore, we evaluate the therapeutic potential of targeting MLVs through lymphangiogenic stimulation or as alternative routes for immune modulation and drug delivery. These approaches offer promising avenues to enhance anti-tumor immunity and may pave the way for next-generation treatment paradigms in GBM.

The tumor microenvironment (TME) is often characterized by distinctive features such as hypoxia, low pH, the overexpression of extracellular matrix-degrading enzymes, and increased redox reactions. These attributes create a specialized internal environment that promotes tumor cell survival and proliferation, thereby facilitating tumor development, metastasis, and the emergence of drug resistance. These challenging aspects pose significant hurdles to the efficacy of traditional cancer therapies. However, they also offer unique opportunities for the development of responsive nanomedicines that specifically target the TME to improve treatment outcomes for cancer patients when combined with photothermal therapy (PTT). This review provides an overview of the predominant features of the TME and delves into recent advancements in the field of nanomedicine, with a special focus on TME-responsive nanomedicines. Each type of TME-responsive nanomedicine is reviewed for its potential value in drug delivery in combination with PTT and chemotherapy, which may enable effective multimodal antitumor therapy. Finally, the review discusses the challenges and opportunities associated with the use of TME-responsive nanomaterials in PTT, highlighting the potential for these innovative strategies to overcome current therapeutic limitations and improve patient outcomes.

Ovarian cancer, a frequently occurring gynecological malignancy with a poor prognosis and a 5-year survival rate below 45%, often progresses due to metastatic colonization. This review highlights the potential of traditional Chinese medicine (TCM) monomers as anticancer agents that inhibit the metastatic colonization of ovarian cancer cells. TCM monomers exhibit various mechanisms of action, including (1) inhibiting epithelial-to-mesenchymal transformation by modulating cell adhesion molecules; (2) reducing extracellular matrix damage through inhibition of degrading enzymes; (3) affecting cytoskeletal dynamics to alter cell movement; and (4) preventing angiogenesis by downregulating angiogenic factors. Additionally, TCM monomers can reshape the tumor microenvironment, enhance immune responses, and induce oxidative stress, resulting in reduced proliferation and survival of cancer cells. The comprehensive action of TCM monomers makes them promising candidates for individualized, multi-target therapies in drug-resistant cases. This paper reviews the current research on the mechanisms through which TCM monomers combat metastatic colonization, aiming to provide insights for future studies and clinical applications in ovarian cancer treatment, ultimately offering hope to affected patients.

This paper comprehensively examines the anticancer mechanisms and therapeutic potential of β-sitosterol, a naturally occurring phytosterol found in various plants. β-Sitosterol has shown significant efficacy in inhibiting tumor growth and metastasis through various biological pathways, including inducing apoptosis, arresting cell cycle progression, and suppressing cell proliferation, invasion, and migration. We highlight the key mechanisms by which β-sitosterol exerts its effects, such as modulating apoptosis-related signaling pathways like those of the Bcl-2 family proteins and reactive oxygen species production. Furthermore, β-sitosterol's role in disrupting the epithelial-mesenchymal transition and its impact on tumor metabolism, particularly in cholesterol and glucose regulation, are discussed. The article also explores the potential of β-sitosterol to enhance chemotherapy sensitivity, making it a promising adjunct in cancer treatment. Additionally, we incorporate a bibliometric analysis and network pharmacology approach to identify potential therapeutic targets and pathways influenced by β-sitosterol, providing new insights into its multifaceted anticancer activities. These findings underscore the potential of β-sitosterol as a novel anticancer agent, warranting further research and clinical investigation to optimize its future therapeutic application.

Non-muscle-invasive bladder cancer (NMIBC) categorizes early-stage urothelial carcinoma that has not invaded the bladder's muscle layer. Although it is initially treatable with transurethral resection, NMIBC has a high risk of recurrence and progression, which necessitates prolonged surveillance and intravesical therapies. Intravesical bacillus Calmette-Guérin (BCG), originally developed as a tuberculosis vaccine, has proven effective in reducing recurrence and delaying progression in NMIBC. Notably, BCG immunotherapy was among the first treatments to demonstrate that activating the immune system could control localized urothelial cancer. Although there has been recent growth in novel intravesical therapies for patients with BCG-unresponsive disease, options remain limited, and radical cystectomy is still frequently performed. Recent advances in systemic therapies, especially immunotherapies targeting the programmed cell death protein 1/programmed death ligand 1 pathway, have now affected NMIBC, with pembrolizumab receiving regulatory approval. This development has spurred numerous clinical trials investigating systemic therapeutic agents in NMIBC alone or in combination with other modalities such as intravesical therapy or radiation to improve outcomes. To understand the current landscape in this clinical space, a systematic review of systemic therapy in NMIBC was performed. Current data and ongoing studies that use systemic agents to treat this disease are presented. Despite recent progress in this domain, there remains a substantial need for more effective treatments with fewer toxicities for NMIBC. Future trials will be essential for optimizing these therapies and improving patient outcomes.

MicroRNAs or miRNAs are characterized as non-coding RNAs, and these are the critical regulators of gene expression post-transcription. Emerging evidence highlights their important role in both the progression and repression of cancer. miRNAs, found in both primary tumor cells and circulation, not only regulate primary tumor development but also regulate metastatic progression by affecting the behavior of primary tumor cells and resident cells at distant organs. Metastasis remains a major clinical challenge in cancer treatment, which limits the therapeutic efficacy and reduces patient survival significantly. This challenge is particularly evident in triple-negative breast cancers (TNBC). This malignancy responds poorly to current chemotherapies and lacks reliable biomarkers, thus, it lacks targeted therapy options. Notably, TNBC exhibits a high propensity for metastasis to critical organs such as the brain, bone, liver, and lung. The process of metastasis of TNBC primary tumor remains unclear, which highlights the critical need to uncover its molecular insights and organ-specific biomarkers. As key regulators of metastasis, microRNAs play a vital role in TNBC progression by modulating gene expression in primary tumor cells and functioning as circulating messenger molecules that affect distant metastatic sites. Furthermore, their potential as therapeutic targets are currently being explored in preclinical models, including the development of anti-miRNA oligonucleotides and miRNA mimics. Overall, this review offers an in-depth mechanism of TNBC metastasis and the molecular mechanisms driving the brain, bone, liver, and lung metastasis. The key focus is on understanding the role of miRNAs in directing organ-specific metastasis and evaluating their potential as biomarker for diagnosis and targeted treatment.

Metastatic melanoma is an aggressive and treatment-resistant skin cancer with a low 5-year survival rate of 27%. Historically considered radioresistant, melanoma's response to radiation therapy (RT) has evolved, especially when integrated with systemic therapies like immune checkpoint inhibitors (ICIs). RT is now recognized for its utility in local control, palliative care, and brain metastasis management. Emerging evidence shows RT's synergy with ICIs through mechanisms like the abscopal effect. This article explores RT's evolving role in metastatic melanoma treatment, focusing on integration with modern therapies and ongoing research into optimizing outcomes.

Systemic therapies for advanced local and metastatic melanoma, typically used for Stage IIB or higher, can broadly be classified into 2 categories: immunotherapies and targeted therapies. Immunotherapies work by inhibiting immune checkpoints (ie, disinhibiting immune checkpoint blockade), resulting in greater T-cell anti-tumor activity. Targeted therapies, reserved for BRAF V600-mutant melanomas, are orally-available small molecules that inhibit the function of activated oncoproteins such as BRAF and MEK. These systemic medications carry a significant risk for adverse effects, often affecting the cutaneous, gastrointestinal and endocrine systems.

Mohs micrographic surgery (MMS) is a tissue-sparing surgical technique that is the standard of care for treatment of several cutaneous malignancies. Current US and international guidelines recommend wide local excision as the first-line surgical therapy for noninvasive melanoma, and use of MMS may be appropriate for melanoma-in-situ, lentigo maligna, and potentially thin invasive malignant melanoma. Based on available literature, MMS can potentially result in lower recurrence rates of melanoma, especially when using immunostaining. This chapter explores the existing evidence supporting MMS for treatment of melanoma as well as its challenges.

Cutaneous melanoma is a highly aggressive malignancy originating from melanocytes. It frequently occurs on the head/neck where it is often diagnosed at advanced stages and associated with poorer outcomes compared to the trunk and extremities. Wide local excision remains the standard-of-care for localized disease; however, Mohs micrographic surgery offers superior local control for melanomas in cosmetically sensitive areas. Sentinel lymph node biopsy remains essential for staging. Recent advances in adjuvant and neoadjuvant therapies have improved survival, while innovations in genetic profiling, prediction tools, and tailored imaging are enhancing personalized treatment, accurate staging and detection, resulting in better patient outcomes.

Genomic advancements have transformed melanoma prognosis by identifying key genetic alterations that influence disease progression and treatment outcomes. Gene expression profiling (GEP) tests, including the 31-GEP, 11-GEP, and 8-GEP + CP, refine traditional staging by stratifying patients based on recurrence and metastasis risk. These tests enhance clinical decision-making by guiding sentinel lymph node biopsy selection, surveillance intensity, and adjuvant therapy use. Studies confirm their prognostic accuracy, linking GEP results to survival outcomes. Despite their potential, challenges like cost and validation limit widespread adoption. As research progresses, integrating genomic data with traditional staging could further personalize melanoma management.

The eighth edition of the AJCC Cancer Staging Manual introduced important updates to melanoma staging to improve prognostic accuracy and guide treatment. However, it has some limitations. Genetic testing, nomograms, and biobanks are becoming important tools for better risk assessment and personalized treatment. While imaging advances are promising, further research is needed to determine if they can replace traditional methods like sentinel lymph node biopsy. Overall, the eighth edition is a step forward, but further improvements and a focus on personalized approaches are needed for better patient outcomes.

Melanoma, an aggressive skin cancer, requires timely diagnostics for improved patient outcomes. The ABCDE criteria-assessing asymmetry, borders, color, diameter, and evolution-serve as foundational guidelines for early detection. Non-invasive tools like dermoscopy, total body photography, and advanced imaging techniques enhance visualization of skin lesions, while artificial intelligence-driven algorithms improve diagnostic accuracy. Despite these advancements, biopsy remains the gold standard for definitive diagnosis. This multifaceted approach highlights the need for integrating traditional methods with innovative technologies to optimize melanoma evaluation and management, ultimately leading to better patient outcomes.