Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing an antitumor immune response; however, recombinant IL-12 has shown significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors, and cellular vectors. Previous studies have found that the fusion of IL-12 with extracellular matrix proteins, collagen, and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses, and poxviruses have been used to deliver IL-12—with testing previously conducted in various cancer models. The local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective antitumor immunity and acting synergistically with other therapies without compromising safety. In addition, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the anti-tumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.

Oncolytic virus (OV) immunotherapy, particularly with oncolytic herpes simplex virus (oHSV), has become a promising new strategy in cancer treatment. This field has achieved significant clinical milestones, highlighted by the FDA approval of Talimogene laherparepvec (T-VEC) for melanoma in 2015 and the approval of Teserpaturev/G47Δ for malignant glioma in Japan in 2021. This review synthesizes the key preclinical and clinical advancements in oHSV therapy over the last decade, critically analyzing the core challenges in target selection, genetic modification, administration routes, and targeted delivery. Key findings indicate that arming oHSV with immunomodulatory transgenes, such as cytokines and antibodies, and combining it with immune checkpoint inhibitors are critical strategies for enhancing therapeutic efficacy. Future research will focus on precision engineering using CRISPR/Cas9, the development of novel delivery vehicles like nanoparticles and mesenchymal stem cells (MSCs), and biomarker-guided personalized medicine, aiming to provide safer and more effective solutions for refractory cancers. This review synthesizes oHSV advances and analyzes novel delivery and gene-editing strategies.

Cancer is one of the major global health burdens, and more effective treatments are needed. At present, there are surgery, targeted therapy, and immunotherapy for the treatment of tumors, but due to the limitations of diagnostic technology and drug resistance, surgery and targeted therapy have little effect. Active immunization in the field of immunotherapy can mobilize host immunity, trigger tumor-specific T-cell responses, and produce targeted cytotoxicity. Its efficacy largely depends on the targeted delivery efficiency of cancer vaccines. Although immunotherapy is more durable than other approaches, immunosuppression in the tumor microenvironment and immune evasion by malignant cells limit the therapeutic efficacy of cancer vaccines. To overcome these challenges, this review summarizes key strategies for improving vaccine vector targeting, as well as recent advances and trends in delivery systems.

Therapeutic cancer vaccines are a new growth point of biomedicine with broad industrial prospects in the post-COVID-19 era. Many large international pharmaceutical companies and emerging biotechnology companies are deploying different tumor therapeutic cancer vaccine projects, focusing on promoting their clinical transformation, and the vaccine industry has strong momentum for development. Such vaccines are also the core engine and pilot site for the development of new vaccine targets, new vectors, new adjuvants, and new technologies, which play a key role in promoting the innovation and development of vaccines. Various therapeutic cancer vaccines, such as viral vector vaccines, bacterial vector vaccines, cell vector vaccines, peptide vaccines, and nucleic acid vaccines, have all been applied in clinical research. With the continuous development of technology, therapeutic cancer vaccines are evolving towards the trends of precise antigens, efficient carriers, diversified adjuvants, and combined applications. For instance, the rapidly advancing mRNA-4157 vaccine is a typical representative that combines personalized antigens with efficient delivery vectors (lipid nanoparticles, LNPs), and it also shows synergistic advantages in melanoma patients treated in combination with immune checkpoint inhibitors. In this article, we will systematically discuss the current research and development status and clinical research progress of various therapeutic cancer vaccines.

KRAS is the most frequently altered oncogenic driver in human cancer. Its mutations drive the initiation and progression of many solid tumors. Clinical validation of covalent KRAS^G12C inhibitors marked a step change and renewed focus on allele-directed strategies and the circuits that regulate KRAS signaling. We summarize recent advances across KRAS structure and conformations, allelic heterogeneity, and roles in signaling, metabolic control, and immune microenvironment remodeling. For direct inhibition, we summarize allele-specific drugs for G12C, G12D and G12V, as well as conformation-selective broad-spectrum inhibitors, outlining design logic and therapeutic outlook. For indirect intervention, we analyze SHP2 and SOS1 inhibition, MEK blockade, metabolic targeting, and immunotherapy combinations, with the biological rationale for each pairing. We also analyze the genetic and phenotypic mechanisms underlying primary and acquired resistance, and discuss counterstrategies such as next-generation inhibitors, rational treatment sequencing, and circulating tumor DNA (ctDNA) monitoring. The KRAS therapeutic landscape is shifting toward conformation-aware, multimodal precision therapy and longitudinal disease management, which providing avenues for durable control of KRAS-mutant tumors.