Lipoprotein‑associated phospholipase A2 (Lp‑PLA2), an important member of the phospholipase A2 superfamily, was originally investigated for its proinflammatory role in cardiovascular diseases. Recent studies have revealed its significant role in tumorigenesis: It can act as either a tumor promoter or a tumor suppressor depending on the context. The present review systematically outlined the dual mechanisms by which Lp‑PLA2 contributes to cancer pathogenesis. As a tumor promoter, it promotes cancer progression via the induction of epithelial‑mesenchymal transition, glutathione peroxidase 4‑mediated resistance to ferroptosis, and vascular endothelial growth factor‑-dependent angiogenesis; conversely, as a tumor suppressor, it inhibits tumor growth by suppressing the Wnt/β‑catenin pathway in breast cancer gene 1‑mutated cancers or by promoting apoptosis. Mechanistic investigations clarify the interactions between Lp‑PLA2 and critical oncogenic pathways, such as the Notch and HIF1α pathways, while emphasizing the functional dichotomy that is influenced by the microenvironment. Current evidence supports the development of microenvironment‑guided targeting strategies and the potential value of Lp‑PLA2 as a prognostic biomarker and therapeutic target. These findings contribute to a theoretical framework for comprehending the context‑dependent roles of Lp‑PLA2 and may guide the development of innovative therapeutic approaches.

To evaluate the association between GSTP1 rs1695 A>G polymorphism and colorectal cancer (CRC) risk in an Iranian cohort, and to validate findings through a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared to CCRT alone in locally advanced cervical cancer (LACC).

To compare the clinical outcomes of thyroid artery embolization (TAE) in the treatment of thyroid nodules.

Small nucleolar RNA host gene 22 (SNHG22) is a novel long non-coding RNA (lncRNA) that functions as an oncogene and promotes the progression of various cancers. This pooled analysis aimed to clarify the prognostic role of SNHG22 in solid tumors and to explore its correlation with disease characteristics.

The GABAergic system, commonly known as the inhibitory system in the central nervous system, also plays a crucial role in cancer development.

The evolution of technology and medicine has allowed for a considerable number of alternatives for treating medical issues, particularly those requiring invasive surgery. Thyroid nodules consisting of abnormal benign tissue are conventionally managed with surgery (lobectomy); however, advancements have introduced radiofrequency ablation as a method to manage these nodules. The two interventions have shown similar efficacies and no conclusive determination has been reported that proves which method (if any) has the lower recurrence rate. Therefore, this systematic review and meta-analysis was designed to fill this information gap.

Adenoid cystic carcinoma (ACC) is a malignant neoplasm arising from the minor and major salivary glands that tend to spread by perivascular and perineural routes. Brain metastases (BM) secondary to ACC are extremely rare, and the standard management strategy has not been well reported due to the rarity. Notably, no previous study has specifically examined the efficacy of stereotactic radiosurgery (SRS) for BM from ACC. We retrospectively reviewed cases of BM from ACC treated with CyberKnife (CK) SRS at our institution between 1998 and 2024. A total of 40 lesions from 5 patients were included. Tumor control was defined based on radiological response to CK SRS as a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) per response evaluation criteria in solid tumors (RECIST) guidelines. The median Follow-up duration was 11 months (Range: 3-51 months). The median age at treatment was 52 years with a male-to-female ration of 3:2. The median maximum diameter of the lesions was 7.mm. The median prescription dose delivered was 24 Gy. The treatment responses at the first follow-up were CR/PR/SD/PD: 9/19/12/0. At the last follow-up, 5 lesions had local progression, with one lesion at 39 months, and 4 lesions at 11 months after CK SRS, while 16 lesions remained CR. The cumulative 3-months, 6-months, and 12-months local control rates were 100%, 100%, and 89%, respectively. To date, this is the largest study examining the efficacy of SRS for ACC BM. Our results showed sufficient local control following the treatment.

ARID1A is a subunit of the SWI/SNF chromatin remodeling complex that plays a dual role in cancer biology as a tumor suppressor or an oncogene dependent on the cellular context. It is frequently found to be altered in gastrointestinal (GI) cancers esophageal, gastric, hepatocellular, pancreatic and colorectal carcinomas. With approximate mutation rates of 19-20% in gastric and colorectal cancers and up to 10% across all tumors. ARID1A regulates gene expression, genomic stability, and major oncogenic pathways like PI3K/AKT and YAP/TAZ. Its loss has been associated with poor prognosis, increased tumor aggressiveness and pronounced resistance to treatment. In gastric carcinoma, the lack of ARID1A correlates with enhanced tumor invasiveness, poor survival, and immune checkpoint expression offering therapeutic interventions with PARP inhibitors and advanced immunotherapies. Similarly in colorectal cancer, ARID1A alterations are related to microsatellite instability (MSI), affecting tumor behavior and immune responses. In contrast, hepatocellular carcinoma in the absence of ARID1A promotes angiogenesis and tumor progression, while pancreatic cancer displays its role in epithelial-mesenchymal transition (EMT) and metastasis by YAP/TAZ pathway activation. Moreover, miRNA-mediated regulation of ARID1A modulates tumor progression and provides resistance to treatment, for instance, miR-129-5p and miR-3613-3p have been implicated in prognosis. Alongside genetic and molecular studies, our bioinformatics analyses reveal considerable heterogeneity in ARID1A mutational signatures and expression across GI cancers, underscoring its stage-specific prognostic and therapeutic implications. The coexistence of truncating and missense variants further highlights the need for mechanistic validation, and integrative pathway analysis to identify synthetic lethal targets and improve the therapeutic strategies. Integrating ARID1A into precision oncology is a promising approach for improving the diagnostic, prognostic, and treatment modalities for patients with ARID1A-deficient cancers.

Ultraviolet (UV) radiation is a key environmental carcinogen implicated in the development of various skin malignancies. Recent studies highlight the pivotal roles of macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (DDT) in UV-induced skin carcinogenesis. This review aims to consolidate current knowledge of how MIF and DDT contribute to tumor initiation and progression under UV stress, with a focus on their biological functions, signaling pathways, and therapeutic potential.

Cancer immunotherapy is a major advancement in the field. It works by stimulating the patient's immune system to recognize and destroy cancer cells. Several different types of cancer immunotherapies have been developed, such as T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies, cancer vaccines, and many others, which can result in sustainable responses in patients with a wide range of metastatic diseases. Additionally, immunotherapy drugs are being combined with chemotherapy and other targeted therapies to treat a variety of cancer types. Despite the promising results, several challenges remain, such as the almost inevitable immune resistance, drug-related toxicity, and the lack of established and reliable predictive biomarkers to predict toxicity and/or discern a patient's response to immunotherapy. In this chapter, we summarize the mechanisms underlying cancer immunotherapy resistance, especially the contributions of phenotypic plasticity and the underlying non-genetic mechanisms. Furthermore, recent developments in preventing relapses following treatment so that the efficacy of immunotherapy can be improved are also briefly discussed. Finally, the positive impact of an interdisciplinary "Team Medicine" approach to personalize cancer immunotherapy for each patient is highlighted.

There have been tremendous advancements in immunotherapy approaches for patients with renal cell carcinoma (RCC) from the initial interleukin-2 era to the current immune checkpoint inhibitor (ICI) combinations. Several ICI-based therapies have greatly improved outcomes for patients with RCC with the potential for durable responses for a subset of patients. In this chapter, we review the data of key frontline ICI-based combinations for RCC in the metastatic setting and recent data on adjuvant immunotherapy. We also discuss recent data on the role of immunotherapy rechallenge following prior ICI treatment as well as emerging novel immunotherapy strategies with chimeric antigen receptor (CAR) T and gut microbiome interventions. Lastly, we highlight a multidisciplinary team-based approach for patients with RCC treated with ICI including management of immune-related adverse events as well as potential role of cytoreductive nephrectomy in an evolving treatment landscape.

This chapter explores systemic treatment strategies for cutaneous melanoma across neoadjuvant, adjuvant, and Stage IV settings. Neoadjuvant therapy aims to reduce tumor burden pre-surgery, primarily using immune checkpoint inhibitors like nivolumab plus ipilimumab, showing promising response rates. Adjuvant therapy, post-resection, leverages immunotherapy (e.g., nivolumab) and targeted therapies (e.g., dabrafenib plus trametinib) to prevent recurrence in high-risk patients, improving relapse-free survival. Stage IV systemic treatment addresses metastatic disease, employing immunotherapy (nivolumab, pembrolizumab) and targeted mitogen-activated protein kinase (MAPK) pathway inhibitors (dabrafenib plus trametinib) for BRAF-mutant cases, while BRAF wild-type patients benefit from nivolumab-relatlimab or combination therapies. Tables summarize key regimens, efficacy, and toxicities. Content aligns with clinical guidelines, with updates on emerging therapies like tumor-infiltrating lymphocytes (TIL). These approaches enhance survival and treatment-free intervals, tailored to mutation status and disease stage.

Breast cancer (BC) is the most prevalent malignancy among women in the United States, affecting approximately 13% of the female population. While advancements in treatment strategies have improved survival rates, significant challenges remain due to tumor heterogeneity, metastatic progression, and acquired resistance to therapy. Recent studies have highlighted the potential of immunotherapy in managing various solid tumors, including BC. This growing interest stems from increasing recognition of the immune system's role in both normal breast tissue and BC development, leading to extensive clinical investigations into BC immunotherapy and its tumor immune landscape. Despite its promise, immunotherapy for BC faces hurdles such as low tumor immunogenicity, inadequate T-cell infiltration, and a highly immunosuppressive tumor microenvironment (TME), which limit its efficacy. Among the available approaches, PD-1/PD-L1 inhibitors have shown clinical benefit in a subset of metastatic BC patients, particularly those with PD-L1-positive tumors, triple-negative BC (TNBC), or high tumor-infiltrating lymphocyte (TIL) levels. Notably, atezolizumab and pembrolizumab have demonstrated durable responses in metastatic TNBC, underscoring their therapeutic potential. Current research is focused on developing combination immunotherapy strategies that can overcome resistance, enhance response rates, and convert non-responders to therapy-sensitive cases. A key area of investigation involves identifying biomarkers that can predict immunotherapy responsiveness, guide salvage therapy in progressive disease, and optimize personalized treatment combinations. This review explores the latest advancements and future directions in BC immunotherapy, including novel combination strategies with vaccines and chemotherapeutics aimed at improving treatment efficacy and patient survival outcomes.

Tumor-infiltrating regulatory T cells (TI-Tregs) are characterized by their abnormal accumulation and heightened immunosuppressive activity. However, the biomechanical mechanisms that govern Treg identity and function through extracellular matrix (ECM) properties remain poorly understood. In three-dimensional culture systems and the tumor microenvironment (TME), increased matrix stiffness and viscoelasticity have been shown to promote Treg differentiation and expansion. Structural remodeling of the ECM, particularly the realignment of collagen fibers and the reduction in effective pore size, significantly enhances Treg migration. Moreover, biomechanical signals derived from the ECM strengthen the oxidative phosphorylation (OXPHOS) metabolic phenotype and immunosuppressive function of Tregs by modulating mitochondrial dynamics. This review provides a comprehensive analysis of the molecular events through which ECM mechanical properties-such as stiffness, viscoelasticity, and topological structure-regulate Treg identity and functionality, as well as the mechanical sensing and response mechanisms employed by Tregs. The potential for targeting Treg mechanosensors and mechanotransduction pathways to develop mechano-immunomodulatory strategies for cancer therapy is also discussed.

The B-cell lymphoma-2 (Bcl-2) family proteins, key regulators of apoptosis, are frequently dysregulated in cancer, tipping the balance of cell survival and apoptosis in favor of survival. The ubiquitin-proteasome system (UPS) is a critical cellular machinery that controls the Bcl-2 levels through regulation of protein stability. This review delves into the intricate interplay between the proteasome and Bcl-2 family members, exploring how proteasome-mediated degradation impacts cell survival and proliferation to influence cancer progression. We discuss the therapeutic potential of targeting the proteasome-Bcl-2 axis, including the use of proteasome inhibitors as anticancer agents. We examine their mechanisms of action, clinical efficacy, and limitations while exploring emerging strategies to overcome these challenges.

Metformin has been the focus of substantial interest in the field of oncology. Although breast cancer is the type of cancer where metformin was most extensively studied through randomized clinical trials (RCTs), none of the previous reviews in this field provided a comprehensive overview of the landscape of RCTs taking into account the phenotype of breast cancer, its staging, and treatment modalities. This scoping review sought to comprehensively map the literature of RCTs focusing on the use of metformin in the treatment of breast cancer and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. The eligibility criteria encompassed all RCTs involving metformin for adult patients with breast cancer, with no constraints regarding context, language, publication date, or outcomes. We included 122 reports from 40 RCTs comprising a total of 5,623 participants and 107 distinct outcomes. The results showed that most studies did not present results by phenotype of breast cancer and highlighted critical gaps and opportunities in the literature. Notably, limited evidence from subgroup analyses within a large RCT suggested potential benefits of metformin in improving overall and disease-free survival among HER2 + participants but not among patients with other phenotypes, a result that requires further investigation. Our findings highlight the potential for considerably expanding the current knowledge base in this field through the retrospective determination of participant phenotypes, facilitating cost-effective and time-efficient individual participant data meta-analyses. Furthermore, we recommend that funding agencies and journals mandate the comprehensive presentation of results from RCTs on breast cancer based on phenotype.

papillary thyroid carcinoma (PTC) as the most common thyroid tumor, tends to invade adjacent organs, especially lymphatic system. This study aimed to evaluate the discrimination performance of ultrasound elastography (USE) in assessing PTC nodule for determination of cervical lymph node metastasis (CLNM).

The central nervous system (CNS) governs critical physiological processes, and its dysregulation drives severe pathologies, particularly glioma, a life-threatening malignancy with limited therapeutic options. β-elemene (ELE), the bioactive compound derived from Curcuma wenyujin, exhibits potent anti-glioma activity as both a monotherapy and in synergy with chemo- or radiotherapy. Beyond glioma, ELE demonstrates therapeutic versatility across CNS disorders, including traumatic brain injury, ischemic stroke, spinal cord injury, neuropathic pain, experimental autoimmune encephalomyelitis, and obesity-associated microbiota-gut-brain axis dysfunction. Mechanistically, modulation of key signaling pathways implicated in neoplastic proliferation, metastasis, neuroinflammation, apoptosis, and oxidative stress positions ELE as a promising candidate for repurposing traditional medicine in modern neurotherapeutics. This review synthesizes ELE's therapeutic efficacy, elucidates the underlying molecular mechanisms, and highlights outstanding questions to guide future research for ELE therapies, advocating for integrating traditional Chinese medicine-driven approaches into modern pharmacological innovation with favorable treatment outcomes.

Chemotherapy is one of the first-line treatment options in cancer patients. Cisplatin (CDDP) is widely used as one of the antineoplastic agents in many cancers. Nevertheless, CDDP resistance is considered as a therapeutic challenge in cancer. Considering the CDDP side effects in normal tissues, prediction of CDDP response helps to select a suitable therapeutic strategy in cancer patients. Sex-determining region Y-box 2 (SOX2) is a critical regulator of tumor growth and embryogenesis that is involved in tumor metastasis, apoptosis, and cell proliferation, through association with other developmental/oncogenic signaling pathways. SOX2 has also a crucial role in CDDP resistance in tumor cells. Therefore, we discussed the role of SOX2 in regulation of CDDP response in tumor cells. It has been reported that SOX2 upregulation through PI3K/AKT, WNT, Hippo, and TGF-β signaling pathways mainly promotes the CDDP resistance in tumor cells. The present review can be an effective step in introducing SOX2 as a prognostic marker as well as a therapeutic target in cancer patients.