Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

Epitranscriptomics has emerged as another level of epigenetic regulation similar to DNA and histone modifications. N⁶-methyladenosine (m⁶A) is one of the most prevalent and abundant posttranscriptional modifications, widely distributed in many biological species. The level of N⁶-methyladenosine RNA methylation is dynamically and reversibly regulated by distinct effectors including methyltransferases, demethylases, histone modification and metabolites. In addition, N⁶-methyladenosine RNA methylation is involved in multiple RNA metabolism pathways, such as splicing, localization, translation efficiency, stability and degradation, ultimately affecting various pathological processes, especially the oncogenic and tumor-suppressing activities. Recent studies also reveal that N⁶-methyladenosine modification exerts the function in immune cells and tumor immunity. In this review, we mainly focus on the regulatory mechanisms of N⁶-methyladenosine RNA methylation, the techniques for detecting N⁶-methyladenosine methylation, the role of N⁶-methyladenosine modification in cancer and other diseases, and the potential clinical applications.

Retinoblastoma is the most common type of eye tumor in infants and children. Current treatments for retinoblastoma include intravenous chemotherapy, intra-arterial chemotherapy, intravitreal chemotherapy, cryotherapy, radiotherapy, and surgery. However, these treatments come accompanied by adverse effects such as the toxic side effects of chemotherapeutic drugs, post-operative complications including blindness after surgery, or other complications caused by radiotherapy. Immunotherapy is more promising for its low toxicity on normal cells and effectively improves the quality of life of patients. Disialoganglioside (GD2), a sphingolipid expressed on the surface of retinoblastoma, is a potential therapeutic target for retinoblastoma. We summarized immunotherapeutic approaches for both preclinical studies and clinical trials of GD2. An anti-GD2 monoclonal antibody (Dinutuximab), which has been approved for the treatment of high-risk neuroblastomas, has shown promising efficacy in improving patients’ prognosis. Additionally, chimeric antigen receptors (CAR)-T therapy, GD2 vaccines and nanoparticles are also potential therapeutics. Finally, we discuss the prospects and current limitations of these immunotherapeutic approaches for treating retinoblastoma, as well as how to address these problems.

Ovarian cancer is the leading cause of death among women diagnosed with female reproductive system cancers. While significant advances have been made in treating various types of cancer, progress in ovarian cancer treatment over the past 20 years has been minimal, and the treatment course of ovarian cancer is not linear. Although many patients initially respond to treatment and may experience tumor regression, 80% of patients relapse after one or multiple chemotherapy sessions. Cytokines play a crucial role in driving tumor progression, relapse, and drug resistance in ovarian cancer. The knowledge of ovarian cancer drug resistance and the function of cytokines in the development of tumor resistance is currently the subject of numerous relevant studies; meanwhile, the specific molecular pathways are being unearthed. Herein, we summarize the recent advancements in cytokine‐associated ovarian cancer drug resistance. In addition, we also present the cytokine targeting drugs in ameliorating ovarian cancer drug resistance. As multi‐effect factors, cytokines can induce multiple pathways to promote tumor progression and overcome extremely complex and heterogeneous living environments. From the perspective of various paths of cytokine function, the emergence of multi‐target drugs might be more promising for conquering ovarian cancer chemotherapy drug resistance.

The function of transmembrane protein 199 (TMEM199) in cancer development has rarely been studied thus far. We report the nuclear localization of the TMEM199 protein and further analyzed the truncated fractions that mediate its nuclear localization. Cut&Tag assay globally explores the nuclear-located TMEM199 functions and tests its influence on the immune checkpoint PD-L1 in vitro and in vivo. Nuclear-located TMEM199 regulates PD-L1 mRNA levels by binding to transcription factors such as IFNGR1, IRF1, MTMR9, and Trim28, which all promote PD-L1 mRNA expression. Our study demonstrates the nuclear localization of TMEM199 and its immune regulation functions in cancer development. We uncovered the nuclear localization of TMEM199. TMEM199 is involved in CD274 mRNA gene expression by the transcriptional regulation of the upstream transcription factors or cofactors of CD274, such as IFNGR1, IRF1, MTMR9, KAT8, and Trim28. The nuclear-located TMEM199 is reported to address the tumor immune microenvironment commanding function.