S. Renuka Jyothi

Gastric cancer (GC) remains a major global health burden, characterized by high mortality and frequent diagnosis at advanced stages. A key driver of its aggressive progression is angiogenesis, predominantly regulated by vascular endothelial growth factor (VEGF). In parallel, microRNAs (miRNAs)—small non-coding RNAs—have emerged as critical post-transcriptional regulators whose dysregulation profoundly contributes to tumor development and progression. This review highlights the intricate interplay between miRNAs and VEGF in GC, focusing on the molecular mechanisms by which specific miRNAs modulate VEGF expression and downstream signaling. Tumor-suppressive miRNAs, such as miR-29a, miR-126, and miR-4316, directly target VEGF-A to inhibit tumor growth and angiogenesis, whereas oncogenic miRNAs, including miR-210, enhance VEGF expression and pro-angiogenic phenotypes. Targeting this miRNA–VEGF axis represents a promising therapeutic strategy through the restoration of tumor-suppressive miRNAs or inhibition of oncogenic counterparts, potentially in synergy with existing treatments. However, clinical translation is challenged by issues related to in vivo delivery, stability, and specificity. Emerging technologies, including nanoparticle-based delivery systems and exosome-mediated transport, are beginning to overcome these obstacles. Integrating miRNA profiling into personalized treatment approaches may offer a new frontier in GC management, enabling targeted interventions to improve patient outcomes.

Colorectal cancer (CRC) remains a major global health burden, with rising incidence and mortality, particularly in developing countries. The tumor microenvironment (TME) plays a critical role in CRC progression by facilitating angiogenesis, immune evasion, and metastasis through complex intercellular communication. Among the key mediators of this communication are exosomes—nano-sized extracellular vesicles—that transport a variety of bioactive molecules, including competing endogenous RNAs (ceRNAs). These ceRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs, act as molecular sponges for microRNAs (miRNAs), thereby regulating gene expression and influencing cancer-related pathways like Wnt/β-catenin and PI3K/Akt. This review explores the emerging role of exosomal ceRNAs derived from the TME in CRC progression, emphasizing their involvement in promoting tumor cell proliferation, invasion, metastasis, and resistance to therapy. By elucidating the intricate crosstalk between exosomal ceRNAs and the TME, we highlight their potential as novel biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in colorectal malignancies. Despite growing interest in exosomes and non-coding RNAs in colorectal cancer (CRC), limited attention has been given to the specific role of exosomal ceRNAs derived from the tumor microenvironment (TME). Existing reviews have predominantly addressed broader aspects of exosomal non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs in general CRC progression, metastasis, or as biomarkers) or focused on exosomal communication in other malignancies. However, the intricate mechanisms by which TME-derived exosomal ceRNAs establish regulatory networks to drive CRC pathology—particularly through miRNA sponging in stromal-tumor crosstalk—remain underexplored and insufficiently synthesized. This review addresses these critical gaps by uniquely emphasizing exosomal ceRNAs sourced from the TME (including CAFs, macrophages, and other stromal components), elucidating their convergent roles in orchestrating proliferation, invasion, immune evasion, and chemoresistance. By integrating recent evidence into a TME-centric framework, we provide novel insights into potential diagnostic and therapeutic applications, advancing beyond general exosomal RNA overviews toward targeted strategies for CRC.

Neoadjuvant therapy is a cornerstone of modern oncology, yet its efficacy is traditionally assessed only after treatment completion, creating a “black box” period where patients may receive ineffective, toxic therapies. This review explores the transformative potential of circulating tumor DNA (ctDNA) as a dynamic biomarker to overcome this limitation. The short half-life of ctDNA allows for real-time, non-invasive monitoring of tumor burden through serial liquid biopsies. A substantial body of evidence across breast, lung, colorectal, and other solid tumors demonstrates that on-treatment ctDNA dynamics are a powerful predictor of pathological response and long-term survival. Rapid ctDNA clearance is strongly associated with favorable outcomes, providing a rationale for treatment de-escalation, while persistent ctDNA identifies non-responders who may benefit from therapy intensification. Despite its promise, the clinical adoption of ctDNA is hindered by challenges including a lack of assay standardization, the existence of low-shedding tumors, and biological confounders like clonal hematopoiesis. The future of precision neoadjuvant care lies in integrating ctDNA with imaging and other biological data within a multimodal framework, leveraging artificial intelligence to guide personalized, response-adapted treatment strategies. This paradigm shift from static to dynamic assessment promises to unlock the full potential of neoadjuvant therapy, maximizing efficacy while minimizing toxicity for individual patients. Graphical Abstract