Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood–brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

Background: COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3⁺ T cell (× 10⁶, MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4⁺ T cell (× 10⁶, MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8⁺ T cell (× 10⁶, MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 10⁶/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 10⁶/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 10⁶, MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4⁺/CD8⁺ ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75). Conclusion: Our meta-analysis revealed significantly lower levels of immune cells (CD3⁺ T, CD4⁺ T, CD8⁺ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.

A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut–liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient’s gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut–liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.

HER2 is highly expressed in a variety of malignant tumors and affects the prognosis of patients, making it a highly sensitive target for cancer therapy. Since the approval of the first HER2 inhibitor, trastuzumab, in 1998, HER2-targeted drugs have rapidly evolved. Currently, targeting HER2 drugs mainly include monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs). This article reviews the development of HER2 inhibitors for various tumors over the past 20 years.

Cancer is a top global public health concern. At present, molecular targeted therapy has emerged as one of the main therapies for cancer, with high efficacy and safety. The medical world continues to struggle with the development of efficient, extremely selective, and low-toxicity anticancer medications. Heterocyclic scaffolds based on the molecular structure of tumor therapeutic targets are widely used in anticancer drug design. In addition, a revolution in medicine has been brought on by the quick advancement of nanotechnology. Many nanomedicines have taken targeted cancer therapy to a new level. In this review, we highlight heterocyclic molecular-targeted drugs as well as heterocyclic-associated nanomedicines in cancer.