Molecularly imprinted polymers (MIPs) and the imprinting technique provide polymeric material with recognition elements similar to natural antibodies. The template of choice (i.e., the antigen) can be almost any type of smaller or larger molecule, protein, or even tissue. There are various formats of MIPs developed for different medical purposes, such as targeting, imaging, assay diagnostics, and biomarker detection. Biologically applied MIPs are widely used and currently developed for medical applications, and targeting the antigen with MIPs can also help in personalized medicine. The synthetic recognition sites of the MIPs can be tailor-made to function as analytics, diagnostics, and drug delivery systems. This review will cover the promising clinical applications of different MIP systems recently developed for disease diagnosis and treatment.

The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes in nascent RNA transcription in response to IR, the AR antagonist enzalutamide, or the combination of the two, we find that enzalutamide treatment significantly decreased expression of canonical AR target genes but had no effect on DDR gene sets in prostate cancer cells. Surprisingly, we also found that the AR is not a primary regulator of DDR genes either in response to IR or at a steady state in asynchronously growing prostate cancer cells. Implications: Our data indicate that the clinical benefit of combining ADT with RT is not due to direct AR regulation of DDR gene transcription, and that the field needs to consider alternative mechanisms for this clinical benefit.

Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) on the surface of reconstructed 3D melanoma and melanocyte models. This is examined in connection with IDO-1 and IL-6 expression in response to IFN-γ or UVB stimulation, both crucial factors of the melanoma tumor microenvironment (TME). Using a polystyrene scaffold, full-thickness human skin equivalents containing fibroblasts, keratinocytes, and melanocytes or melanoma cells were developed. The samples were stimulated with IFN-γ or UVB, and Trp and Kyn secretion was measured using HPLC-PDA and HPLC-MS. The expression of IDO-1 and IL-6 was measured using RT-qPCR. Increased Trp catabolism to Kyn was observed in IFN-γ-stimulated melanoma and melanocyte models, along with higher IDO-1 expression. UVB exposure led to significant changes in Kyn levels but only in the melanoma model. This study demonstrates the potential of skin surface Trp and Kyn monitoring to capture TME metabolic changes. It also lays the groundwork for future in vivo studies, aiding in understanding and monitoring skin cancer progression.

Spherical, multicellular aggregates of tumor cells, or three-dimensional (3D) tumor models, can be grown from established cell lines or dissociated cells from tissues in a serum-free medium containing appropriate growth factors. Air–liquid interfaces (ALIs) represent a 3D approach that mimics and supports the differentiation of respiratory tract and skin 3D models in vitro. Many 3D tumor cell models are cultured in conjunction with supporting cell types, such as fibroblasts, endothelial cells, or immune cells. To further mimic the in vivo situation, several extracellular matrix models are utilized to support tumor cell growth. Scaffolds used for 3D tumor cell culture growth include both natural and synthetic hydrogels. Three-dimensional cell culture experiments in vitro provide more accurate data on cell-to-cell interactions, tumor characteristics, drug discovery, metabolic profiling, stem cell research, and diseases. Moreover, 3D models are important for obtaining reliable precision data on therapeutic candidates in human clinical trials before predicting drug cytotoxicity. This review focuses on the recent literature on three different tissue types of 3D tumor models, i.e., tumors from a colorectal site, prostate, and skin. We will discuss the establishment of 3D tumor cell cultures in vitro and the requirement for additional growth support.

Langerhans cells (LCs) are primary immune sentinels at barrier surfaces, acting as the first line of defence against foreign pathogens. However, their low abundance within the human epidermis severely limits their availability for functional and mechanistic studies. To address this challenge, we sought to provide a versatile experimental framework for generating, identifying, and characterizing distinct subsets of LCs derived from in vitro differentiation of human peripheral monocytes. LCs’ heterogeneity has long been considered, with recent studies classifying them into four subsets: effector LCs (LC1) and regulatory LCs (LC2) present at steady state, along with activated LCs (aLC) and migratory LCs (migLC) found during skin inflammation. In this study, LC1, LC2, and aLC/migLC subsets were identified by flow cytometric profiling of CD207, CD1a, CD83, and CD197. LC phenotype was further confirmed by examining HLA-DR, CD14, CD209, CD1b, and CD1c expression. Additionally, the phagocytic capacity of LCs relative to distinct macrophage polarizations was evaluated. From the in vitro-generated LCs, the subsets LC1, LC2, and a joint aLC/migLC cluster were identified. LC1 constituted the predominant population, appearing at higher proportions than both LC2 and the aLC/migLC cluster. The proportions of LC2 and aLC/migLC remained relatively consistent across donors, whereas LC1 abundance showed greater variation, suggesting a higher donor-dependent heterogeneity. Overall, LCs exhibited the lowest phagocytic capacity compared with the different macrophage polarizations. Our study defines LC subsets that can be generated from peripheral monocytes in vitro and provides a framework for deeper exploration of human LC biology, subset heterogeneity, and function in both normal and pathological skin.

Replicating the complex physiology of human skin in vitro remains a challenge for cutaneous oncology. Although several three-dimensional (3D) skin and melanoma models have been developed, reproducible skin equivalent systems that enable direct and standardized comparisons between healthy and melanoma-containing skin remain valuable experimental tools. This study aimed to optimize and characterize skin equivalents containing either melanocytes or melanoma cells and to evaluate their utility as platforms for investigating melanoma-associated skin biology and UVB-induced responses in vitro. To achieve this, 3D skin equivalents containing fibroblasts, keratinocytes, and either melanocytes or melanoma cells were reconstructed on a polystyrene scaffold to generate healthy (mc) and melanoma (mm) models. Morphological characteristics were compared with clinically verified human tissue sections, and functional responses to UVB irradiation were assessed with a focus on the kynurenine pathway. The models demonstrated a distinct dermal–epidermal architecture and distinguishable melanoma-associated features, including epidermis-confined melanoma cell clusters, in mm constructs. UVB exposure induced differential responses between models, including significant differences in kynurenine pathway regulation. These findings suggest that the developed skin equivalents provide a reproducible in vitro platform for studying melanoma-associated skin biology and treatment-related metabolic responses and may support future mechanistic studies of skin cancer progression.