Promiscuous Anticancer Drugs from Pathogenic Bacteria: Rational Versus Intelligent Drug Design

Microbial-based therapy of cancer: Current progress and future prospects

“…Azurin induces apoptosis through complex formation with tumor suppressor protein p53 or inhibits growth of cancer cells by interfering in receptor tyrosine kinase-mediated cell signaling or preventing angiogenesis. 150 In vivo cancer regression by azurin has also been demonstrated. The ability of a single bacterial protein, azurin, to interfere in the growth of cancer, is an interesting example of a potential drug candidate that can target multiple unrelated targets, interfering in multiple steps in the disease progression.…”

Bioengineered bugs, drugs and contentious issues in patenting

“…2 Cancer cells are normally resistant to undergoing apoptotic cell death due to mutational inactivation or epigenetic silencing of the expression of genes encoding tumor suppressor proteins such as p53. Azurin promotes apoptotic cell death in cancer cells through complex formation and stabilization of p53.…”

“…20 FDA-approved and currently used anticancer drugs, particularly rationally designed drugs, have a single or limited number of targets, such as one or two receptor tyrosine kinases. 2 The cancer cells respond to such drugs by quickly changing the target, thereby becoming drug resistant. Cardiotoxicity or other forms of toxicity are also often problematic in prolonged use of such drugs because the rationally designed tyrosine kinase inhibitors inhibit other physiologically important tyrosine kinases, of which there are 518 in the human kinome, as well.…”

“…Cardiotoxicity or other forms of toxicity are also often problematic in prolonged use of such drugs because the rationally designed tyrosine kinase inhibitors inhibit other physiologically important tyrosine kinases, of which there are 518 in the human kinome, as well. 2 It would be interesting to see if azurin will be less susceptible to resistance development because of its multi-targeting nature as well as its mode of inhibition of the tyrosine kinase (preventing ligand binding rather than occupying the ATP-binding pocket). 2 It is to be noted that azurin can also prevent cancer emergence as judged by its ability to inhibit (70%) precancerous lesion formation in growing normal mammary cells, when such cells are exposed to a carcinogen such as 7,12-dimethyl-benzanthracene (DMBA), in murine mammary organ culture (MMOC) assays.…”

“…In this article, because of my past experience and the importance of creating and protecting intellectual property (IP) generated by scientific research through the legal system, I dwell at length on my involvement and the complexities associated with the patenting process 1 and some of my current research requiring patent protection. 2 …”