A first-in-class, first-in-human phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with metastatic refractory solid tumors.

New targeted approaches against the ubiquitin–proteasome system in gastrointestinal malignancies

“…bolus followed by 2 weeks of rest. A promising tumor response rate was observed in eight out of 14 patients (57%) [90]. Other related Hdm2 compounds include the HLI98 molecules that specifically inhibit the RING-finger domain of Hdm2, not the regions that interact with p53 [91].…”

Overcoming drug resistance in multi-drug resistant cancers and microorganisms

“…Of the 15 patients treated with p28, stabilization of disease occurred in 6 patients, partial regression of tumor in 2 patients, and complete regression of the tumors in 2 other patients, without demonstrating any toxicity or side effects even at the highest dose ( Table 2). 33 Besides its anti-neoplastic abilities, the azurin protein also inhibits the growth of other infectious agents, including the malarial parasite Plasmodium falciparum, the toxoplasmosis-causing parasite Toxoplasma gondii and the human AIDS virus HIV-1. 32 Our research has also uncovered other bacterial proteins and peptides with potential activity against pathogens and cancers.…”

Patent controversies and court cases

“…p28 has not only cancer preventive property, but in phase I human clinical trials in 15 stage IV cancer patients (Table 1), it was shown to be non-toxic even at the highest dose where it demonstrated significant cancer regressing effects, including partial and complete regressions in some cases, in such patients with drug-resistant cancers. 9 The effect of p28 on cancer stem cells has not yet been studied and its mode of cancer preventive action is unknown. The next step would be to demonstrate the cancer preventive ability of p28 in mouse models where tumors such as glioblastomas 14 or lung cancers 15,16 can be triggered in mice with viral vectors harboring activated oncogene mutations such as H-RAS, AKT, TP53 or K-RAS.…”

“…We have recently addressed this issue by demonstrating that a bacterial protein, and a peptide derived from it, have not only demonstrated anticancer activity including entry specificity in cancer cells but in laboratory experiments demonstrate cancer preventive activity as well. [6][7][8] Coupled with the fact that a chemically-synthesized peptide derived from such a protein (azurin), termed p28, demonstrated in phase I human clinical trials very little toxicity in 15 advanced stage (stage IV) cancer patients, allowing partial or sometimes complete regression of drug-resistant tumors in some patients ( Table 1), 9 and also demonstrated cancer preventive activity in laboratory experiments (Fig. 1), 7,8 it would be of great interest to examine any cancer preventive effect of p28 in vulnerable women with BRCA1/BRCA2 mutations 6 or high-risk people with PALB2 mutations for pancreatic cancer or even other cancers such as glioblastoma multiforme.…”