MicroRNA (miRNA) are small noncoding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. The dysregulation of miRNA has been implicated in numerous human diseases, including cancers. miR-34 family members (miR-34s), including miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.

This review discusses reprogramming the breast tumor immune microenvironment from an immunosuppressive cold state to an immunologically active hot state. A complex interplay is revealed, in which the accumulation of metabolic byproducts—such as lactate, reactive oxygen species (ROS), and ammonia—is shown to impair T-cell function and promote tumor immune escape. It is demonstrated that the tumor microenvironment (TME) is dominated by immunosuppressive cytokines, including interleukin-10 (IL-10), transforming growth factorβ (TGFβ), and IL-35. Notably, IL-35 is produced by regulatory T cells and breast cancer cells. The conversion of conventional T cells into IL-35-producing induced regulatory T cells, along with the inhibition of pro-inflammatory cytokine secretion, contributes to the suppression of anti-tumor immunity. It is further demonstrated that key immune checkpoint molecules—such as PD-1, PDL1, CTLA-4, TIM-3, LAG-3, and TIGIT—are upregulated within the TME, leading to Tcell exhaustion and diminished immune responses. The blockade of these checkpoints is shown to restore T-cell functionality and is proposed as a strategy to convert cold tumors into hot ones with robust effector cell infiltration. The therapeutic potential of chimeric antigen receptor (CAR)T cell therapy is also explored, and targeting specific tumor-associated antigens, such as glycoproteins and receptor tyrosine kinases, is highlighted. It is suggested that CART cell efficacy can be enhanced by combining these cells with immune checkpoint inhibitors and other immunomodulatory agents, thereby overcoming the barriers imposed by the immunosuppressive TME. Moreover, the role of the microbiome in regulating estrogen metabolism and systemic inflammation is reviewed. Alterations in the gut microbiota are shown to affect the TME, and microbiome-based interventions are proposed as an additional means to facilitate the cold-to-hot transition. It is concluded that by targeting the metabolic and immunological pathways that underpin immune suppression—through combination strategies involving checkpoint blockade, CART cell therapies, and microbiome modulation—the conversion of the breast TME from cold to hot can be achieved. This reprogramming is anticipated to enhance immune cell infiltration and function, thereby improving the overall efficacy of immunotherapies and leading to better clinical outcomes for breast cancer patients.

MicroRNAs (miRNAs)-based therapies hold great promise for cancer treatment, challenges such as expression variability, off-target effects, and limited clinical effectiveness have led to the withdrawal of many clinical trials. This review investigates the setbacks in miRNA-based therapies by examining miR-21, miR-34, and miR-155, highlighting their functional complexity, off-target effects, and the challenges in delivering these therapies effectively. Moreover, It highlights recent advances in delivery methods, combination therapies, and personalized treatment approaches to overcome these challenges. This review highlights the intricate molecular networks involving miRNAs, particularly their interactions with other non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), emphasizing the pivotal role of miRNAs in cancer biology and therapeutic strategies. By addressing these hurdles, this review aims to steer future research toward harnessing the potential of miRNA therapies to target cancer pathways effectively, enhance anti-tumor responses, and ultimately improve patient outcomes in precision cancer therapy.

Melanoma, a highly aggressive form of skin cancer, poses a significant global health burden, with 331,647 new cases and 58,645 deaths reported in 2022. The development of melanoma is influenced by various factors, including sunlight exposure and BRAF^V600 mutations that activate the MAPK/ERK pathway. The introduction of BRAF and MEK inhibitors has revolutionized the treatment landscape for melanoma patients. However, innate and acquired therapeutic resistance remains a significant challenge. This review provides a comprehensive overview of the current state of BRAF-targeted therapies in melanoma, highlighting the efficacy and limitations of FDA-approved combinations of BRAF and MEK inhibitors such as vemurafenib, dabrafenib, trametinib, and cobimetinib. The review also explores the off-target effects of BRAF inhibitors on endothelial cells, emphasizing the need for more selective therapies to minimize vascular complications and metastatic potential. The article also discusses potential druggable targets, including ERK5, CD73, ALDH1A1, PLA1A, and DMKN, which are promising in addressing diagnostic hurdles and guiding personalized therapeutic decisions. Recent studies on regorafenib, ERK5 signaling, and CD73 inhibition are highlighted as novel strategies to overcome resistance and improve treatment outcomes. The review also delves into the role of advanced therapeutic tools, such as mRNA vaccines and CRISPR-Cas9, in revolutionizing personalized oncology by targeting specific genetic mutations and enhancing immune responses against melanoma. The ongoing synergy between advancing research, targeted interventions, strategic treatment combinations, and cost-effectiveness evaluations offers a promising pathway to elevate patient outcomes in the persistent battle against melanoma significantly.

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) are widely used as gene editing tools in biology, microbiology, and other fields. CRISPR is composed of highly conserved repetitive sequences and spacer sequences in tandem. The spacer sequence has homology with foreign nucleic acids such as viruses and plasmids; Cas effector proteins have endonucleases, and become a hotspot in the field of molecular diagnosis because they recognize and cut specific DNA or RNA sequences. Researchers have developed many diagnostic platforms with high sensitivity, high specificity, and low cost by using Cas proteins (Cas9, Cas12, Cas13, Cas14, etc.) in combination with signal amplification and transformation technologies (fluorescence method, lateral flow technology, etc.), providing a new way for rapid detection of pathogen nucleic acid. This paper introduces the biological mechanism and classification of CRISPR-Cas technology, summarizes the existing rapid detection technology for pathogen nucleic acid based on the trans cleavage activity of Cas, describes its characteristics, functions, and application scenarios, and prospects the future application of this technology.

MicroRNA (miRNA) is small non-coding RNAs that play vital roles in post-transcriptional gene regulation by inhibiting mRNA translation or promoting mRNA degradation. Dysregulation of miRNA has been implicated in numerous human diseases, including cancers. The family members of miR-34 (miR-34s), composed of miR-34a, miR-34b, and miR-34c, have emerged as the most extensively studied tumor-suppressive miRNAs. In this comprehensive review, we aim to provide an overview of the major signaling pathways and gene networks regulated by the miR-34s in various cancers and highlight the critical tumor suppressor role of miR-34s. Furthermore, we will discuss the potential of using miR-34 mimics as a novel therapeutic approach against cancer, while also addressing the challenges associated with their development and delivery. It is anticipated that gaining a deeper understanding of the functions and mechanisms of miR-34s in cancer will greatly contribute to the development of effective miR-34-based cancer therapeutics.