Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical and mechanical signals between cells and their environment in a wide range of states in health and diseases. Integrin functions are dependable on a delicate balance between active and inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, and trafficking. Due to their exposure on the cell surface and sensitivity to the molecular blockade, integrins have been investigated as pharmacological targets for nearly 40 years, but given the complexity of integrins and sometimes opposite characteristics, targeting integrin therapeutics has been a challenge. To date, only seven drugs targeting integrins have been successfully marketed, including abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, and carotegrast. Currently, there are approximately 90 kinds of integrin-based therapeutic drugs or imaging agents in clinical studies, including small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, imaging agents, etc. A serious lesson from past integrin drug discovery and research efforts is that successes rely on both a deep understanding of integrin-regulatory mechanisms and unmet clinical needs. Herein, we provide a systematic and complete review of all integrin family members and integrin-mediated downstream signal transduction to highlight ongoing efforts to develop new therapies/diagnoses from bench to clinic. In addition, we further discuss the trend of drug development, how to improve the success rate of clinical trials targeting integrin therapies, and the key points for clinical research, basic research, and translational research.

Metastasis to bone frequently occurs in majority of patients with advanced breast cancer and prostate cancer, leading to devastating skeletal-related events and substantially reducing the survival of patients. Currently, the crosstalk between tumor cells and the bone stromal compartment was widely investigated for bone metastasis and the resistance to many conventional therapeutic methods. Osteopontin (OPN), also known as SPP1 (secreted phosphoprotein 1), a secreted and chemokine-like glyco-phosphoprotein is involved in tumor progression such as cell proliferation, angiogenesis, and metastasis. The expression of OPN in tumor tissue and plasma has been clinically proved to be correlated to poor prognosis and shortened survival in patients with breast cancer and prostate cancer. This review summarizes the multifaceted roles that OPN plays in bone microenvironment and drug resistance, with emphasis on breast and prostate cancers, via binding to αvβ3 integrin and CD44 receptor and inducing signaling cascades. We further discuss the promising therapeutic strategy for OPN targeting, mainly inhibiting OPN at transcriptional or protein level or blocking it binding to receptor or its downstream signaling pathways. The comprehending of the function of OPN in bone microenvironment is crucial for the development of novel biomarker and potential therapeutic target for the diagnosis and treatment of bone metastasis and against the emergence of drug resistance in advanced cancers.

Objective In patients with asthma and chronic obstructive pulmonary disease (COPD), disease control is still suboptimal—incorrect inhalation technique and medication non‐adherence are two important reasons for this outcome. Pharmacists' interventions have been shown to have a positive effect on the clinical outcomes of asthma and COPD. Quantitative assessment of the efficacy of pharmacist‐led interventions, mainly on inhalation techniques and medication adherence, is needed. Evidence for different interventions is not totally conclusive, and no results of theory‐based adherence promotion interventions for asthma and COPD have been published. The objective of our study is to evaluate the effect of pharmacist‐led interventions on asthma and COPD management, focusing mainly on inhalation technique and medication adherence, and whether the content of interventions (categorized based on Information‐Motivation‐Behavioural skills (IMB) model) affects the effectiveness and whether the IMB model is worthy of clinical promotion and application in adults with asthma or COPD. Methods The PubMed, EMBASE, The Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched for randomized controlled trials that involved pharmacist‐led interventions among patients with asthma or COPD. We used database‐specific vocabulary (eg, Medical Subject Headings) and free text terms expanding from ‘asthma’, ‘COPD’ and ‘pharmacist’ to identify relevant articles. Two reviewers independently selected the studies, assessed the risk of bias and extracted the data. The meta‐analysis was performed in Review Manager 5.3 provided by the Cochrane Collaboration. PROSPERO registration number: CRD42019144793. Results and discussion Thirteen studies were eligible for qualitative analysis, and 12 studies were included in the meta‐analysis. Pharmacist‐led interventions showed a positive effect on medication adherence (1.34 [95% CI 1.18‐1.53], P < .0001) and inhalation technique (1.85 [95% CI 1.57‐2.17], P < .00001) in COPD and asthma patients. In the subgroup meta‐analysis, significant medication adherence improvement was found only in COPD patients (1.41 [1.24‐1.61], P < .0001). The subgroup meta‐analysis also noted that interventions that included all three Information‐Motivation‐Behavioural skills (IMB) constructs had a significant improvement in medication adherence (1.41 [1.24‐1.61], P < .0001). Subgroup meta‐analysis conducted between different diseases, different intervention contents, and different measure tools did not significantly change the heterogeneity. What is new and conclusion Pharmacist‐led interventions can improve inhalation technique in adult asthma and COPD patients. Significant improvement in medication adherence was found only in COPD patients. The effect among asthmatic patients requires further study. Interventions based on the IMB model may be worthy of clinical promotion and application. More future research is needed to establish solid evidence base for effective interventions and uniform measurement of medication adherence.

Integrins are main cell adhesion receptors serving as linker attaching cells to extracellular matrix (ECM) and bidirectional hubs transmitting biochemical and mechanical signals between cells and their environment. Integrin αvβ3 is a critical family member of integrins and interacts with ECM proteins containing RGD tripeptide sequence. Accumulating evidence indicated that the abnormal expression of integrin αvβ3 was associated with various tumor progressions, including tumor initiation, sustained tumor growth, distant metastasis, drug resistance development, maintenance of stemness in cancer cells. Therefore, αvβ3 has been explored as a therapeutic target in various types of cancers, but there is no αvβ3 antagonist approved for human therapy. Targeting-integrin αvβ3 therapeutics has been a challenge, but lessons from the past are valuable to the development of innovative targeting approaches. This review systematically summarized the structure, signal transduction, regulatory role in cancer, and drug development history of integrin αvβ3, and also provided new insights into αvβ3-based therapeutics in cancer from bench to clinical trials, which would contribute to developing effective targeting αvβ3 agents for cancer treatment.

Chronic liver diseases, primarily metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and metabolic dysfunction-associated alcoholic liver disease (MetALD), and viral hepatitis, can lead to liver fibrosis, cirrhosis, and cancer. Hepatic stellate cell (HSC) activation plays a central role in the development of myofibroblasts and fibrogenesis in chronic liver diseases. However, HSC activation is influenced by the complex microenvironments within the liver, which are largely shaped by the interactions between HSCs and various other cell types. Changes in HSC phenotypes and metabolic mechanisms involve glucose, lipid, and cholesterol metabolism, oxidative stress, activation of the unfolded protein response (UPR), autophagy, ferroptosis, senescence, and nuclear receptors. Clinical interventions targeting these pathways have shown promising results in addressing liver inflammation and fibrosis, as well as in modulating glucose and lipid metabolism and metabolic stress responses. Therefore, a comprehensive understanding of HSC phenotypes and metabolic mechanisms presents opportunities for novel therapeutic approaches aimed at halting or even reversing chronic liver diseases.