Upper tract urothelial cancer (UTUC) are rare subsets of urothelial cancer, which typically present with more aggressive course. Molecular markers stratifying urothelial tumors as luminal subtype and non-luminal subtype tumors have been proposed to select patients who may have greater or lesser benefit from neoadjuvant systemic therapy in bladder cancer, though not yet evaluated in UTUC. Here, a single-institution study retrospectively obtained clinical and genomic information in patients with UTUC and evaluated four patient tumors using the Decipher Bladder^® assay and Foundation Medicine^® test. All four patients had non-luminal molecular subtype including basal (N = 4) and mixed basal/claudin-low (N = 2) subtypes. The best clinical response achieved was stable disease in a patient who had basal/claudin-low subtype with residual ypT3 after neoadjuvant chemotherapy. For the remaining three patients, all were treated with platinum-based chemotherapy for eventual metastatic disease but all three showed progressive disease with limited overall survival, highlighting their aggressive course. The non-luminal subtype and lack of FGFR alteration may partly explain the poor overall outcomes while the real-world benefit of next generation sequencing for clinical use in UTUC patients require further clarification in a larger cohort study.

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.

Oral squamous cell carcinoma (OSCC) is a highly malignant and invasive tumor with significant mortality and morbidity. Current treatment modalities such as surgery, radiotherapy, and chemotherapy encounter significant limitations, such as poor targeting, systemic toxicity, and drug resistance. There is an urgent need for novel therapeutic strategies that offer targeted delivery, enhanced efficacy, and reduced side effects. The advent of lipid-based nanoparticles (LNPs) offers a promising tool for OSCC therapy, potentially overcoming the limitations of current therapeutic approaches. LNPs are composed of biodegradable and biocompatible lipids, which minimize the risk of toxicity and adverse effects. LNPs can encapsulate hydrophobic drugs, improving their solubility and stability in the biological environment, thereby enhancing their bioavailability. LNPs demonstrate significantly higher ability to encapsulate lipophilic drugs than other nanoparticle types. LNPs offer excellent storage stability, minimal drug leakage, and controlled drug release, making them highly effective nanoplatforms for the delivery of chemotherapeutic agents. Additionally, LNPs can be modified by complexing them with specific target ligands on their surface. This surface modification allows the active targeting of LNPs to the tumors in addition to the passive targeting mechanism. Furthermore, the PEGylation of LNPs improves their hydrophilicity and enhances their biological half-life by reducing clearance by the reticuloendothelial system. This review aims to discuss current treatment approaches and their limitations, as well as recent advancements in LNPs for better management of OSCC.

Immune checkpoint inhibitors (ICI)-based combinations have become the standard first-line treatment for advanced clear cell renal cell carcinoma (ccRCC). Despite significant improvements in survival and the achievement of sustained long-term responses, a subset of patients remains refractory to ICI, and most will eventually develop resistance. Thus, identifying predictive biomarkers for ICI efficacy and resistance is essential for optimizing therapeutic strategies. Up to now, tissue-based biomarkers have not been successful as predictive biomarkers in RCC. Circulating blood-based biomarkers offer a promising alternative. These biomarkers, including circulating immune cells, soluble factors, tumor-derived markers, and those based on metabolomics, are less invasive, offer reproducibility over time, and provide a comprehensive assessment of tumor biology and patient immune status, as well as allow dynamic monitoring during treatment. This review aims to evaluate the current evidence on the different candidate circulating biomarkers being investigated for their potential to predict ICI efficacy in RCC patients.

For a long time, the family of receptor tyrosine kinases, including epidermal growth factor receptor and insulin-like growth factor 1 receptor, was regarded as the main players stimulating cell proliferative signaling. Today, it is increasingly clear that many G protein-coupled receptors (GPCRs) are also involved in controlling the hallmarks of cancer by activating diverse intracellular signaling networks. GPCRs can therefore be considered as promising drug targets for fighting against diverse types of human malignancies. Although plant polyphenols, flavonoids, are well known for their diverse anticancer effects inhibiting the growth, proliferation, migration, and invasion of malignant cells, involvement of GPCRs in these activities has still remained largely unelucidated. Therefore, in this review article, the current knowledge about the role of GPCRs in anticancer action of structurally varied flavonoids is compiled, highlighting the ability of these natural polyphenols to modulate the expression levels of GPCRs but also suppress the action of endogenous ligands and downstream tumor-promoting events. These data show that targeting the respective GPCRs by specific flavonoids may open new perspectives in the therapeutic intervention in human malignancies.

Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.