Cancer‐associated fibroblasts (CAFs), a phenotypically and functionally heterogeneous stromal cell, are one of the most important components of the tumour microenvironment. Previous studies have consolidated it as a promising target against cancer. However, variable therapeutic efficacy—both protumor and antitumor effects have been observed not least owing to the strong heterogeneity of CAFs. Over the past 10 years, advances in single‐cell RNA sequencing (scRNA‐seq) technologies had a dramatic effect on biomedical research, enabling the analysis of single cell transcriptomes with unprecedented resolution and throughput. Specifically, scRNA‐seq facilitates our understanding of the complexity and heterogeneity of diverse CAF subtypes. In this review, we discuss the up‐to‐date knowledge about CAF heterogeneity with a focus on scRNA‐seq perspective to investigate the emerging strategies for integrating multimodal single‐cell platforms. Furthermore, we summarized the clinical application of scRNA‐seq on CAF research. We believe that the comprehensive understanding of the heterogeneity of CAFs form different visions will generate innovative solutions to cancer therapy and achieve clinical applications.

The skin interfaces with the external environment, acting as both a physical barrier and an immunologic defense. The dynamic interactions between various cell types are essential for skin homeostasis and function. Emerging research has unveiled the significant role of extracellular vesicles (EVs) as key mediators of cell communication in regulating many aspects of skin physiological and pathological processes. In this review, we provide an overview of recent advances in understanding the physiological and pathological roles of EVs in skin health, aging, and diseases, and discuss natural and engineered EVs in skin disease treatment along with the potential challenges. The burgeoning area of EVs may expand new therapeutic approaches for various skin disorders and open new avenues for personalized skincare treatments.

Extracellular vesicles (EVs) are nanoscale, lipid bilayer-enclosed particles containing bioactive molecules that play crucial roles in tissue homeostasis. These vesicles regulate cellular functions via delivery of protein, lipid, and nucleic acid cargos to target cells, thereby orchestrating essential biological processes, including cellular proliferation, activation, angiogenesis, and immune responses. The past decade has witnessed unprecedented growth in research examining EV functions in cutaneous physiology and pathogenesis. Here, we describe the biogenesis, composition and cellular uptake of EVs, critically highlighting the therapeutic effects and potential mechanisms of EVs from mammalian, plant and bacterial cells in skin diseases, including skin wound healing, hair growth, aging, inflammatory diseases and cancers. In addition, we discuss clinical translation challenges and outline future research directions for advancing EV-based therapeutics in clinical dermatology.

The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

The skin epidermis, with its capacity for lifelong self-renewal and rapid repairing response upon injury, must maintain an active status in metabolism. Mechanistic target of rapamycin (mTOR) signaling is a central controller of cellular growth and metabolism that coordinates diverse physiological and pathological processes in a variety of tissues and organs. Recent evidence with genetic mouse models highlights an essential role of the mTOR signaling network in epidermal morphogenesis and barrier formation. In this review, we focus on the recent advances in understanding how mTOR signaling networks, including upstream inputs, kinases and downstream effectors, regulate epidermal morphogenesis and skin barrier formation. Understanding the details of the metabolic signaling will be critical for the development of novel pharmacological approaches to promote skin barrier regeneration and to treat epidermal barrier defect-associated diseases.