Cancer cell: a new cancer treatment target found in mitochondria, which is expected to treat blood cancer

May 4, 2019 / Biovalley / a study by the Anderson Cancer Center at the University of Texas has identified a new therapeutic target for cancer cells and explained how a new anticancer drug called imiridines works by inducing cancer cell death in blood cancers such as acute myeloid leukemia (AML) and mantle cell lymphoma This study revealed a target in mitochondria, called caseinolytic protease P (CLPP), which breaks down the proteins in mitochondria when it is activated This process is called mitochondrial proteolysis A new anticancer drug called imipridones has been shown to activate CLPP and cause cancer cell death through mitochondrial protein hydrolysis Photo source: http://cn.bing.com no matter what form the common tumor suppressor p53 exists, onc201 and onc212 can play a role The study, led by Michael andreeff, MD, Professor of leukemia, and Dr Jo ishizawa, assistant professor of leukemia, was published in cancer cell on May 2 "Despite the existence of new targeted drugs, most hematological and solid tumors are still incurable This basically includes all patients with p53 mutations, "andreeff said "Therefore, there is an urgent need for antitumor drugs with new mechanisms of action, and our findings support the clinical development of imipiridones and other CLPP activators for the treatment of human cancer." Through in vitro and in vivo models, the team demonstrated that knockout of CLPP or overexpression of inactivated CLPP can induce cancer cells to be fully resistant to onc201 and onc212, indicating that the activation of CLPP is essential for drug-induced cell death Through extensive crystallographic studies, the team identified the exact binding sites and patterns of the drugs on CLPP and showed how they increased protease activity Although onc201 is still in the early stage of clinical trials in the treatment of acute myeloid leukemia and other cancers, its preclinical efficacy has been confirmed in many cancer models, but the direct goal behind its success is still difficult to determine Preclinical toxicology studies have been conducted on onc212, and researchers plan to conduct clinical trials in the near future "The absence or mutation of CLPP has never been reported in primary AML cases, suggesting that CLPP may be an effective target for AML molecular and cytogenetic subsets," ishizawa said Our data show that patients with the lowest CLPP levels are less sensitive to CLPP hyperactivity Therefore, CLPP level can be used as a biomarker to identify AML patients who are most likely to respond to this treatment " Andreeff said further studies are needed in more patients to determine the threshold of CLPP expression that is most likely to predict a patient's response to treatment Reference: Michael andreeff et al Mitochondrial CLPP mediated proteolysis causes selective cancer cell lethality Cancer cell Doi: https://doi.org/10.1016/j.ccell.2019.03.014