The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. Significance: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747

Currently, the outbreak of COVID-19 is rapidly spreading especially in Wuhan city, and threatens 14 million people in central China. In the present study we applied the Moran index, a strong statistical tool, to the spatial panel to show that COVID-19 infection is spatially dependent and mainly spread from Hubei Province in Central China to neighbouring areas. Logistic model was employed according to the trend of available data, which shows the difference between Hubei Province and outside of it. We also calculated the reproduction number R0 for the range of [2.23, 2.51] via SEIR model. The measures to reduce or prevent the virus spread should be implemented, and we expect our data-driven modeling analysis providing some insights to identify and prepare for the future virus control.

The PROteolysis TArgeting Chimeras (PROTACs) is an innovative technique for the selective degradation of target proteins via the ubiquitin–proteasome system. Compared with traditional protein inhibitor drugs, PROTACs exhibit advantages in the efficacy and selectivity of and in overcoming drug resistance in cancer therapy, providing new insights into the discovery of anti-cancer drugs. In the last two decades, many PROTAC molecules have been developed to induce the degradation of cancer-related targets, and they have been subjected to clinical trials. Here, we comprehensively review the historical milestones and latest updates in PROTAC technology. We focus on the structures and mechanisms of PROTACs and their application in targeting tumor-related targets. We have listed several representative PROTACs based on CRBN, VHL, MDM2, or cIAP1 E3 ligases, and PROTACs that are undergoing anti-cancer clinical trials. In addition, the limitations of the current research, as well as the future research directions are described to improve the PROTAC design and development for cancer therapy.

Chemotherapy is the main clinical treatment method of gastric cancer. Multidrug resistance (MDR) has become a common phenomenon with the development of tumors, which alleviates the effect of chemotherapy and makes it difficult to break the bottleneck of survival rate of advanced gastric cancer. Therefore, the exploration of MDR reversal agents for gastric cancer is the focus and also the difficulty of current treatment. Currently, the researches on the mechanisms of drug resistance in gastric cancer have been continuously deepened, which reveal different pathways and targets of MDR, laying a solid foundation for studying reversal agents. As a kind of natural medicine, traditional Chinese medicine (TCM) owns the characteristics of low toxicity, high safety and effectiveness. It can inhibit the occurrence, growth and metastasis of tumors, and reverse MDR via multiple pathways and mechanisms, the pathological function of which has become a research hotspot in recent years. TCM reversers are mainly divided into Chinese medicine monomers, Chinese patent medicines, and Chinese herbal compounds. With certain quantity and advantage, TCM reversers for MDR play an important role in the clinical treatment and show great potential in gastric cancer.

Targeted protein degradation (TPD) represents a paradigm shift in drug discovery, moving beyond traditional binding‐based inhibition toward active removal of disease‐driving proteins. This approach has unlocked therapeutic possibilities for previously “undruggable” targets, including transcription factors like MYC and STAT3, mutant oncoproteins such as KRAS G12C, and scaffolding molecules lacking conventional binding pockets. Among TPD strategies, proteolysis‐targeting chimeras (PROTACs) have emerged as the leading clinical platform, with the first molecule entering trials in 2019 and progression to Phase III completion by 2024. This comprehensive review examines PROTAC development across diverse therapeutic areas, analyzing key targets including kinases, hormone receptors, antiapoptotic proteins, and epigenetic modulators. We evaluate clinical progression of breakthrough candidates such as ARV‐110 for prostate cancer, ARV‐471 for breast cancer, and BTK degraders, while discussing critical challenges including the “hook effect” and oral bioavailability limitations. The review explores future directions encompassing innovative delivery strategies, tissue‐specific degrader design, and approaches for expanding E3 ligase repertoires and overcoming resistance. This review provides essential foundations for rational target selection, molecular optimization, and clinical translation strategies. By integrating mechanistic insights with clinical realities, this analysis offers perspectives on PROTAC technology advancement and identifies opportunities for transforming treatment of complex diseases resistant to conventional therapies.