Immune checkpoints are critical in modulating immune responses and maintaining self-tolerance. Cancer cells can exploit these mechanisms to evade immune detection, making immune checkpoints attractive targets for cancer therapy. The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer treatment, with monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1 demonstrating clinical success. However, challenges such as immune-related adverse events, primary and acquired resistance, and high treatment costs persist. To address these challenges, it is essential to explore alternative strategies, including small-molecule and peptide-based inhibitors, aptamers, RNA-based therapies, gene-editing technologies, bispecific and multispecific agents, and cell-based therapies. Additionally, innovative approaches such as lysosome-targeting chimeras, proteolysis-targeting chimeras, and N-(2-hydroxypropyl) methacrylamide copolymers are emerging as promising options for enhancing treatment effectiveness. This review highlights significant advancements in the field, focusing on their clinical implications and successes.

Anti-cancer drugs can be toxic to healthy cells in the body and have the potential to cause irreversible damage to ovarian tissue. This may lead to premature ovarian insufficiency. There are two main strategies to preserve fertility in women undergoing chemotherapy treatment for cancer. One is controlled ovarian hyperstimulation with gonadotropins and a protective agent for safety, followed by freezing of oocytes or embryos; the other is ovarian suppression using gonadotropin-releasing hormone agonists (GnRH agonists). This review aims to gain an understanding of the best way to support women with cancer to preserve their fertility. As breast cancer is the most common cancer in women worldwide, it is the primary focus of this review.

The expanding clinical utilization of immune checkpoint inhibitors (ICIs) in oncology has brought increasing attention to thyroid dysfunction as a prominent immune-related adverse event (irAE). Elucidating the pathophysiological mechanisms underlying ICI-induced thyroiditis represents a critical step toward developing evidence-based diagnostic protocols and targeted therapeutic interventions for cancer patients undergoing immunotherapy. This comprehensive review systematically examines current advances in understanding the etiopathogenesis of ICI-induced thyroiditis. First, we described pharmacological characterization of ICIs, then discussed multifactorial analysis of cellular and molecular contributors to thyroid autoimmunity following ICI administration and finally analyzed critical evaluation of emerging hypotheses regarding primary pathogenic drivers. Through this review, we aim to establish mechanistic connections between ICI pharmacodynamics and thyroid tissue immunopathology.

Tumor cells can utilize the immune checkpoint pathway to inhibit T cell activation and evade the attack of tumor specific T cells. While immune checkpoint inhibitors (ICIs) competitively bind to checkpoint molecules to block checkpoint mediated suppression of the immune system. Immune checkpoint inhibitors have emerged as a milestone in cancer immunotherapy, demonstrating significant efficacy in various cancers. However, their clinical application still faces challenges such as low response rates (<30% in solid tumors), significant side effects, and suppression by the tumor microenvironment. Nanomaterials offer new solutions to optimize the therapeutic effects of ICIs. This article explores the potential of combining nanomaterials with ICIs in cancer treatment.

Type 1 diabetes (T1D) is an autoimmune-mediated disorder that leads to the destruction of pancreatic beta-cells, insulin deficiency, and chronic hyperglycemia. It is one of the most common childhood endocrine disorders. Recent evidence indicates that aberrant Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling exacerbates T1D by promoting the production of proinflammatory cytokines and chemokines. By blocking JAK-mediated phosphorylation of STAT proteins, JAK inhibitors help alleviate cytokine-driven inflammation, reduce insulin requirements, and relieve complications such as painful peripheral neuropathy, potentially preserving residual beta-cell function and improving glycemic control. Moreover, emerging data underscore the potential synergy between JAK inhibitors and immune checkpoint therapies targeting the programmed cell death protein 1 (PD-1) pathway, as PD-1/Programmed cell death ligand 1 (PD-L1) inhibitors used in antitumor therapy can induce immune checkpoint inhibitor-induced diabetes (CPI-DM). This review examines the impact of JAK inhibitors on beta-cells and immune cells in T1D, along with their safety profiles and adverse effects. It explores the potential benefits and risks of combining JAK inhibitors in the management of CPI-DM associated with anti-PD-1/PD-L1 therapy. In conclusion, while JAK inhibitors have demonstrated the potential to reduce inflammation and preserve beta-cell function in preclinical studies, further clinical trials are needed to confirm their long-term safety and efficacy in patients with T1D and CPI-DM.

Aurora kinases, AURKA, AURKB, and AURKC, are serine/threonine kinases that play a vital role in regulating cell division and mitosis, particularly in the separation of chromosomes. These kinases are often overexpressed in human tumor cell lines, indicating their potential involvement in tumorigenesis. Preliminary evidence supports the use of Aurora kinase inhibitors for certain types of tumors, several AURKs inhibitors are currently under phase I and II trials. As a result, there is a growing interest in identifying small-molecule Aurora kinase inhibitors to develop as anti-cancer agents. The regulation of the cell cycle, including mitosis, is increasingly recognized as a key target in the fight against various forms of cancer. Novel drugs are being designed to inhibit the function of regulatory proteins, such as Aurora kinases, with the goal of creating personalized treatments. This review summarizes the biology of Aurora kinases in the context of cancer, integrating both preclinical and clinical data. It discusses the challenges and opportunities associated with using Aurora kinases to enhance cancer treatment. Future directions for Aurora kinase-based therapies include developing more selective inhibitors that minimize off-target effects and improve therapeutic efficacy. Researchers are also exploring combination therapies that use Aurora kinase inhibitors alongside other targeted treatments to overcome resistance and improve patient outcomes. Additionally, advancements in biomarker discovery are expected to facilitate the identification of patients most likely to benefit from Aurora kinase-targeted therapies, paving the way for more personalized approaches to cancer treatment.

Immunotherapy, including immune checkpoint inhibition, has transformed the prognosis of many patients with cancer. However, most patients have primary or secondary resistant tumors to currently available cancer immunotherapies. Changes in glycosylation of malignant cells and in the tumor microenvironment are a new target to overcome resistance to current cancer immunotherapies and to improve the outcome of patients. Here, we summarize how changes in glycosylation in cancer have functional consequences on the immune system. Such changes can be directly targeted with drugs. Moreover, they can mediate immune-suppressive effects. For example, increased sialylation can enhance interactions with immune-inhibitory Siglec receptors, and galectin-mediated interactions can modulate immune responses in the context of cancer. Finally, we provide an overview of approaches to therapeutically target these changes for the improvement of cancer immunotherapy.

SLFN11, a DNA/RNA helicase implicated in replication stress response, has recently emerged as a pivotal determinant of chemotherapy sensitivity across multiple cancer types. The expression level of SLFN11 in various cancers is significantly positively correlated with the sensitivity of cancer cell DNA damage agents. SLFN11 exerts its chemosensitizing effects by RPA-coated single-stranded DNA (ssDNA) at stressed replication forks at stalled replication forks, thereby potentiating the cytotoxicity of platinum agents, topoisomerase inhibitors, and PARP inhibitors. Its roles in inhibiting ATR translation, mediating p53-independent apoptosis, sensitizing towards IFN-γ and enhancing chromatin accessibility also remain investigational. The down-regulation of SLFN11 expression is associated with epigenetic silencing including promoter methylation, histone deacetylation, and the histone methylation. In this paper, we reviewed the recent progress of SLFN11 as predictive biomarker and therapeutic target in multiple cancers including medulloblastoma, prostate cancer, breast cancer, ovarian cancer, lung cancer, head and neck cancer, esophageal carcinoma, gastric carcinoma and colorectal cancer. We also summarized 10 active clinical trials conducting molecular analyses to assess SLFN11's role. By bridging mechanistic understanding with translational opportunities, this review provides a roadmap for leveraging SLFN11 to overcome chemoresistance and advance precision oncology.

Colorectal cancer (CRC) is among the most prevalent malignant tumors in the digestive system and is the third leading cause of cancer-related mortality. In recent years, immunotherapy has markedly enhanced the objective response and survival rates for CRC patients. However, the therapeutic efficacy of immunotherapy remains insufficient for the majority of proficient mismatch repair (pMMR) CRC patients, with 20% to 30% of deficient mismatch repair (dMMR) patients demonstrating poor responses or developing drug resistance. Increasing evidence underscores the critical role of intestinal microorganisms in modulating the effectiveness of immunotherapy, particularly in regulating the tumor microenvironment (TME).

There is a continuous increase in the incidence of thyroid cancer. A deeper understanding of the molecular mechanisms of thyroid cancer could significantly improve thyroid cancer management. Newly discovered type of programmed cell death, ferroptosis, has been demonstrated to play a crucial role in many cancers. Mounting evidence shows that there is a close association between ferroptosis and thyroid cancer, which offer a promising therapeutic strategy for thyroid cancer. Ferroptosis is expected to emerge as a novel therapeutic target. Regrettably, the exact role of ferroptosis in thyroid cancer is not yet completely understood. Further, there is currently no summary of ferroptosis in thyroid cancer progression and treatment. Hence, in this review, we aim to revisit the pathological process of thyroid cancer and reveal the role of ferroptosis in thyroid cancer. In addition, we provide evidence that ferroptosis inducers could suppress the growth of thyroid cancer cells. Lastly, we discuss the potential application of ferroptosis inducers in thyroid cancer treatment, as well as possible impediments and corresponding strategies. The relationship between ferroptosis and thyroid cancer will be better understood through this review, which may offer a novel insight into thyroid cancer therapy.

Menin inhibitors, which target the KMT2A-menin protein-protein interaction to inhibit blasts proliferation and induce differentiation, have demonstrated potential effects on acute leukemia subtypes characterized by overexpression of HOXA gene cluster and MEIS1 (including KMT2A rearrangements, NPM1 mutations, NUP98 rearrangements and other genetic alterations). Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.

Pinostrobin (PIN), a natural flavonoid found in Boesenbergia rotunda, Alpinia zerumbet, and other botanicals, has shown promising anticancer potential due to its multitargeted mechanisms and favorable safety profile. This review consolidates current evidence on PIN's anticancer properties, focusing on its molecular mechanisms, pharmacokinetics (PKs), and therapeutic potential. A systematic literature search was conducted using PubMed, Scopus, ScienceDirect, and Google Scholar to identify preclinical studies on PIN's bioactivity, PK, and toxicity. PIN exerts potent anticancer effects by inducing ROS-mediated apoptosis, cell cycle arrest via p21 upregulation and cyclin D1 suppression, and reducing proliferation and inducing cytotoxicity. It also inhibits metastasis by targeting migration, adhesion, and angiogenesis. PK data reveal good intestinal absorption and metabolic transformation primarily, although limited solubility and brain penetration remain challenges. Toxicity studies show no adverse effects at therapeutic doses (≤ 100 mg/kg), with selective cytotoxicity against cancer cells and protective antioxidant effects in normal tissues. Beyond oncology, PIN also exhibits several pharmacological properties. PIN's ability to target key cancer pathways, along with its low toxicity and broad pharmacological potential, makes it a strong candidate for adjuvant therapy. The novelty of this study is its integrated analysis of PIN's anticancer mechanisms, PK, and safety, along with proposed strategies to bridge the gap toward clinical application. Clinical trials remain essential to confirm its efficacy.

PurposeTo comprehensively evaluate the efficacy and safety of combining poly (ADP-ribose) polymerase (PARP) inhibitors with chemotherapy in patients with advanced breast cancer.MethodsA systematic literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) evaluating PARP inhibitor-chemotherapy combinations. Studies reporting progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety outcomes were included. Data extraction and quality assessment were performed independently by two reviewers, and a meta-analysis was conducted using random-effects models.ResultsOf 970 studies retrieved, four RCTs involving 1064 patients met the inclusion criteria. PARP inhibitors combined with chemotherapy significantly improved PFS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.84, P < .0001) and showed a trend towards improved OS (HR 0.93, 95% CI 0.79-1.09, P = .36), though this was not statistically significant. There was no significant improvement in ORR (RR 1.08, 95% CI 0.98-1.20, P = .13). Regarding safety, no significant difference was observed in all grades or grade 3-4 adverse events (AEs) overall, but the combination therapy was associated with an increased risk of anemia, nausea, and diarrhea (RRs ranging from 1.14 to 1.29, all P < .01).ConclusionPARP inhibitor combined with chemotherapy is an effective option for the treatment of patients with advanced breast cancer, but its potential increased risks of specific AEs need to be weighed. Clinicians should make individualized treatment plans according to the specific conditions of patients, comprehensive consideration of efficacy and safety.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become key agents in the treatment of hormone receptor positive (HR +), human epidermal factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). In combination with endocrine therapy, CDK4/6 inhibitors are currently considered first-line treatment for HR + /HER2- MBC. There are three CDK4/6 inhibitors currently available: palbociclib, ribociclib and abemaciclib. The toxicity profiles of the CDK4/6 inhibitors are well-detailed in the respective clinical trials and post-marketing reports. This review will detail the hepatotoxic effects of CDK 4/6 inhibitors and how the incidence rate compares among agents.

Cancer remains one of the most deadly diseases in the world, requiring constant growth and improvements in therapeutic strategies. Traditional cancer treatments, such as chemotherapy, radiotherapy, and surgery, have limitations like off-target release, toxicity, and inefficient drug delivery. This study explains the role of bioinformatics and AI in optimizing and analyzing liposomal formulations for innovative and better cancer therapy. Molecular docking (MD), molecular dynamics simulations, and machine learning models are the computational techniques that can help to design stable liposomal carriers for drugs, predict receptor-ligand interactions, and can improve drug release efficiency. Improved liposome nanoparticles (LNPs) surface functionalization, the discovery of tumor-specific biomarkers, and the improvement of receptor-ligand interactions for accurate drug targeting are all made possible by bioinformatics tools and methodologies. Moreover, AI-assisted predictions and in silico modeling can speed up drug discovery and processing while eliminating the experimental expenditures and time. In the present review, we conducted MD studies to complement the discussed literature. MD was performed between cyclic RGD peptides (liposomal ligands) and the GPR116 receptor in triple-negative breast cancer, and between folic acid (liposomal ligand) and the Axl tyrosine kinase receptor for lung cancer, revealing strong and stable interactions and highlighting the amino acid residues involved. Notwithstanding current obstacles, computational tools have shown notable progress in nanomedicine, exploring more options for more individualized and effective cancer therapies. The combination of AI, machine learning, and multi-omics techniques to improve therapeutic efficacy and reduce side effects is a substantial key to the future of LNP-based cancer treatment.

Basal cell carcinoma (BCC) is a prevalent form of skin cancer that can be localized or metastatic. Current evidence supports the use of Hedgehog (Hh) pathway inhibitors for locally advanced or metastatic BCC with resistance due to genetic alterations in the Hh pathway. This systematic review evaluated the prevalence of genetic alterations in Hh pathway genes in BCC.

Could the next major advancement in cancer therapy stem from utilizing the body's own cells to precisely deliver potent anti-cancer agents directly to tumors? This innovative strategy, known as cell-drug conjugates (CDCs), represents a transformative approach to targeted cancer treatment by leveraging the inherent biological properties of cells. Leveraging the inherent biological properties of cells, these conjugates enable highly specific drug delivery and enhance therapeutic efficacy. Through mechanisms such as chemotaxis and immune evasion, CDCs can transport anticancer agents across biological barriers and selectively accumulate within the tumor microenvironment, facilitating precision therapy. Various cell types, including red blood cells, stem cells, and immune cells, serve as potential carriers in these systems, each possessing unique biological characteristics and antitumor ability. At present, there are few reviews on the preparation and function of CDCs in cancer therapy. This review systematically explores CDC applications in cancer therapy, including targeting mechanisms, fabrication strategies,in vivopharmacology, and clinical advancements. Furthermore, the review examines the technical challenges associated with this innovative drug delivery and therapeutic strategy, while also evaluating its potential for clinical translation.

The premetastatic niche (PMN) represents a metastasis-facilitative microenvironment established prior to tumor dissemination, initiated by vascular leakage and endothelial cell (EC) functional remodeling. ECs play pivotal roles as bridges in different stages of the metastatic cascade. As critical stromal components within the PMN, ECs not only drive angiogenesis but also actively orchestrate immune suppression, extracellular matrix (ECM) remodeling, and the inflammatory signaling characteristic of PMN formation, with multiple specific signaling pathways such as VEGF/Notch playing a crucial role. With the evolving understanding of the role of ECs in controlling tumor metastasis, therapeutic strategies targeting ECs within the PMN, such as antiangiogenic therapy (AAT), targeting of endothelial glycocalyx (GCX), inhibition of tumor-derived exosome (TDE) and angiocrine signaling, are becoming research hotspots. This review systematically delineates the cellular and molecular composition of PMNs, dynamically dissects their spatiotemporal evolution, and highlights organ-specific mechanisms of EC-driven PMN establishment. Furthermore, we summarize emerging EC-targeted therapeutic strategies, providing innovative insights for inhibiting tumor metastasis.

Chemotherapy is one of the most frequent therapeutic options in cancer patients. Cisplatin (CDDP) is widely used as one of the first-line platinum-based drugs in metastatic tumors. However, CDDP resistance is always one of the main therapeutic challenges in cancer patients. Considering the side effects of CDDP in cancer patients, the prediction of CDDP response can improve the management of tumor therapy. Therefore, it is necessary to investigate the molecular mechanisms involved in CDDP resistance in order to predict CDDP response in cancer patients. CDDP resistance is contributed with different cellular processes such as DNA repair, drug efflux, and signaling pathways. WNT/β-catenin pathway has a key role in tumor growth and drug resistance. β-catenin is considered as a key component of the WNT pathway, which can regulate the CDDP response in tumor cells by regulation of WNT target genes. In addition to the WNT pathway, β-catenin can also be regulated by the other signaling pathways. Deregulation of β-catenin is associated with CDDP resistance. Therefore, in the present review, we discussed the role of β-catenin in regulation CDDP response in tumor cells. It has been reported that β-catenin mainly promotes CDDP resistance in various cancers, whose function can be affected by other signaling pathways and transcription factors. This review can be an effective step toward introducing β-catenin as a prognostic marker as well as a therapeutic target in CDDP-resistant cancer patients.

Genomic instability is a hallmark of cancer and is associated with tumor progression and therapeutic resistance. Centrioles and centrosomes are a critical determinant of genomic stability. Polo-like kinase 4 (PLK4) is a serine-threonine kinase that plays a critical role in the regulation of centrosome duplication. PLK4 overexpression drives tumorigenesis and has been shown to be overexpressed in a wide variety of human tumors, where it is associated with more advanced disease and worse clinical outcomes. As such, there has been significant interest in pharmacologically targeting PLK4 using small-molecule inhibitors for therapeutic gain in multiple cancer types. In this review, we will discuss the functions of PLK4 in normal and oncogenic processes. We will further discuss the current state of PLK4 as a therapeutic target in cancer by reviewing the current literature on PLK4 inhibitors in both the preclinical and clinical space. Finally, we will discuss the emerging data exploring rational combinations of PLK4 inhibitors with DNA-damaging agents and immunotherapies as a means to unlock the potential of these agents in cancer therapy.