Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for the sequential activation of downstream targets, such as MEK and the transcription factor ERK, which control numerous cellular and physiological processes, including organism development, cell cycle control, cell proliferation and differentiation, cell survival, and death. Defects in this signaling cascade are associated with diseases such as cancer. RAF inhibitors (RAFi) combined with MEK blockers represent an FDA-approved therapeutic strategy for numerous RAF-mutant cancers, including melanoma, non-small cell lung carcinoma, and thyroid cancer. However, the development of therapy resistance by cancer cells remains an important barrier. Autophagy, an intracellular lysosome-dependent catabolic recycling process, plays a critical role in the development of RAFi resistance in cancer. Thus, targeting RAF and autophagy could be novel treatment strategies for RAF-mutant cancers. In this review, we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and RAFi-resistance. Furthermore, we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic profiles. Additionally, this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer. 

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

High-throughput quantitative detection of triple-negative breast cancer-associated expressed miRNAs by rolling circle amplification on fluorescence-encoded microspheres

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF4/NaYF4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8+ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8+-T-cell-targeted NaYbF4/NaYF4 nanoparticles and H-2Kb/ovalbumin257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies. 

Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses.

A state-of-the-art review on solid lipid nanoparticles as a nanovaccines delivery system

The poly (lactic-co-glycolic acid) (PLGA) based nanoparticles have been applied for drug delivery due to their simple preparation, biodegradability, and ideal biocompatibility. In this study, the factors affecting the degradation of PLGA-based nanoparticles are reviewed, encompassing the ratio of PLA to PGA, relative molecular weight, crystallinity, and preparation process of PLGA nanoparticles. The drug release behavior of PLGA-based nanoparticles, such as the degradation environment, encapsulated drug properties of polymers, and drug loading rates, are also discussed. Since gastrointestinal cancer is one of the major global threats to human health, this paper comprehensively summarizes the application of PLGA nanoparticles in gastrointestinal cancers from diagnosis, chemotherapy, radiotherapy, and novel tumor treatment methods (immunotherapy, gene therapy, and photothermal therapy). Finally, the future application of PLGA-based drug delivery systems in treating gastrointestinal cancers is discussed. The bottleneck of application status and the prospect of PLGA-nanoparticles in gastrointestinal tumor application are presented. To truly realize the great and wide application of PLGA-based nanoparticles, collaborative progress in the field of nanomaterials and life sciences is needed. 

The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers

A novel therapeutic vaccine based on graphene oxide nanocomposite for tumor immunotherapy

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A novel therapeutic vaccine based on graphene oxide nanocomposite for tumor immunotherapy