Next-Generation Anti-Angiogenic Therapies as a Future Prospect for Glioma Immunotherapy; From Bench to Bedside.

Glioblastoma (grade IV glioma) is the most aggressive histopathological subtype of glial tumors with inordinate microvascular proliferation as one of its key pathological features. Extensive angiogenesis in the tumor microenvironment supplies oxygen and nutrients to tumoral cells; retains their survival under hypoxic conditions; and induces an immunosuppressive microenvironment. Anti-angiogenesis therapy for high-grade gliomas has long been studied as an adjuvant immunotherapy strategy to overcome tumor growth. In the current review, we discussed the underlying molecular mechanisms contributing to glioblastoma aberrant angiogenesis. Further, we discussed clinical applications of monoclonal antibodies, tyrosine kinase inhibitors, and aptamers as three major subgroups of anti-angiogenic immunotherapeutics and their limitations. Moreover, we reviewed clinical and preclinical applications of small interfering RNAs (siRNAs) as the next-generation anti-angiogenic therapeutics and summarized their potential advantages and limitations. siRNAs may serve as next-generation anti-angiogenic therapeutics for glioma. Additionally, application of nanoparticles as a delivery vehicle could increase their selectivity and lower their off-target effects.

Clinical theranostics applications of photo-acoustic imaging as a future prospect for cancer.

Photoacoustic imaging (PAI) of biological tissue has been a fast developing biomedical multi-wave imaging modality, after its introduction in the mid90s. PAI couples laser excitation to acoustic detection. Especially, in recent years its significant advantages in onco-surgery has attracted much attention due to its ability to detect malignant tissues. Monitoring cancer angiogenesis, assessment of blood oxygen saturation, functional brain imaging, evaluation of cortical blood volume, detection of skin/conjunctival melanoma depth, assessment of met-hemoglobin, investigating tumor hypoxia andcancer lymph node metastases are some of its promising applications. Moreover, as a real-time monitoring strategy, PAI allows intraoperative imaging of micro-metastases and residual islands in onco-surgery. Herein, we provide a brief introduction to biophysics and fundamentals of PAI, potential novel endogenous and exogenous contrast agents, and novel techniques to develop engineered and targeted contrast agents with theranostic applications. We also summarize the clinical trial pipelines for PAI. Furthermore, we discuss the potential obstacles and limitation of PAI theranostic agents for further clinical applications and strategies to overcome these hurdles.