AVA6000 mention1 Feb 2022 20:45
AVA6000 mentioned can some of our scientists comment please..
5.1.5. Novel Anthracyclines: AVA6000
A first-in-human study has been initiated with AVA600 for patients with locally advanced and/or metastatic solid tumors including CRC (NCT04969835). This promising phase I study will evaluate the safety, tolerability, and pharmacokinetics of AVA6000, a modified pro-drug version of doxorubicin that remains inactive until it reaches the malignant microenvironment. There, once activated as doxorubicin, it attacks malignant cells, triggering multifactorial toxicity that involves oxidative stress by induction of O2•- and H2O2, DNA/RNA damage by binding and blocking topoisomerases, autophagy and apoptosis induction by calcium leakage and calcium channel dysregulation, and mitochondrial dysfunction through •NO release [126].
https://mdpi-res.com/d_attachment/cancers/cancers-13-05037/article_deploy/cancers-13-05037-v2.pdf
6. Conclusions
The involvement of oxidative stress in the tumorigenic process is still a controversial topic. ROS produced either by tumor cells or by TME cells have very diverse and sometimes opposing effects on the evolution of cancer. Low to moderate ROS levels promote cell proliferation, EMT, and angiogenesis. Conversely, high ROS levels favor apoptosis, cell death, and cellular damage. Moreover, ROS influence the immune response against tumors, as they are used by macrophages and neutrophils to destroy cancer cells and activate T and NK cells. Overall, the effects seem to depend on ROS levels, the cancer stage, and the differential outcomes seen in tumor cells because of ROS exposure.
Such a duality of ROS effects in cancer cells and TME allows us to assume that their modulation can be exploited for cancer prevention and treatment. On the one hand, antioxidants could counteract the deleterious consequences of ROS. On the other hand, pro-oxidants could induce ROS-dependent cancer cell death. However, the results do not seem to be conclusive at this point in either case. Further research is needed to provide insights on the role of ROS modulators in the initiation and progression of CRC.
Researchers with AVA6000
126. Songbo, M.; Lang, H.; Xinyong, C.; Bin, X.; Ping, Z.; Liang, S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol. Lett. 2019, 307, 41–48. [CrossRef]
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