This is another pathway to develop against cancer. It is easy to describe, but as usual not so easy to implement. Have not seen that before have we?
I have taken heart with our merging understanding of IV C in large doses as proactive form of Chemo therapy that targets all aspects and types of cells while also blocked by normal cells. Thus we naturally extend the whole toolkit against cancer in general. If it works for all cancers, then cancer is cured.
We may be that close. .
Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics
Ahmed M.E. Abdalla,1,2,* Lin Xiao,1,5,* Muhammad Wajid Ullah,1,5 Miao Yu,3 Chenxi Ouyang,4 and Guang Yang1,5,✉
With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.
Keywords: Cancer, tumor vessels, tumor microenvironment, anti-angiogenic agents, nanotherapeutics, drug resistance, biomarkers, metastasis.
There are many different types of therapies for cancer treatment. However, the choice of cancer therapy is determined by various factors such as the types of tumors (benign or malignant), the stage of diagnosis, and the potential ability of the patient to tolerate the prescribed treatments 1. At present, surgical resections are coupled with chemotherapy or radiotherapy to avoid the occurrence and growth of invisible occult microscopic tumors, even after complete surgical resection 2. However, these conventional strategies (i.e., chemotherapy and radiation) for cancer treatment have poor specificity, dose sensitivity and bioavailability. Furthermore, they do not greatly differentiate between cancerous and normal cells 3. As a result of continual treatment, the cancerous cells susceptible to certain drugs become resistant against them, which leads to further complications such as multidrug resistance (MDR), a situation where conventional therapies fail due to the resistance of tumor cells to one or more drugs 4.
One of the frontiers in the fight against cancer is the regulation of angiogenesis, i.e., the emergence of new blood vessels. Targeting angiogenesis can be an effective approach to prevent the development of new blood vessels and is an essential modality for normalizing the tumor-associated vasculature. Thus, it can prevent the development of tumors and can serve as a complementary therapeutic paradigm for cancer therapy 5, 6. However, different disease progression patterns can be induced by anti-angiogenic therapies, which may lead to worse outcomes in terms of drug resistance, invasion, and metastasis 7. In addition, the poor oral availability and short half-life of such therapies necessitate their regular parenteral administration 8. Currently, it is often attractive for medical applications to design therapeutic monitoring, targeted delivery and controlled drug release into a single platform 9. Owing to the unique properties of nanoparticles (NPs), nanotherapeutics have the potential to provide a more effective and safe mode to circumvent the discrepancies associated with conventional cancer therapies 10, 11. Moreover, “intelligent” vehicles possessing specific physicochemical properties (e.g., size, shape, and surface chemistry) and biological entities (protein, small interfering RNA (siRNA)) can be designed by manipulating nanocarrier characteristics to support therapeutic agents to avoid the clearance mechanisms of the living systems 12. Therefore, the association of anticancer drugs with NPs may provide a sensible method for the delivery and prevention of drug resistance 13, 14.In this review, we first attempt to focus on the nature of tumor vessels and how they can be normalized under current conditions with anti-angiogenic agents in light of their benefits. Next, we describe the pitfalls associated with tumor abnormality and anti-angioge