Science: small peptide double attack on ovarian cancer

In a new study, researchers from a number of research institutions in Norway and the United States found that two modifiers derived from pentapeptide fragments of a natural protein in human body can significantly reduce tumor size in metastatic ovarian cancer model animals This peptide, called psaptide, activates a response that targets tumor cells directly, and also plays a role in healthy tissues, making the tumor microenvironment unsuitable for metastasis These findings suggest that psaptide can be used as a promising template to develop therapeutic options against ovarian cancer and possibly other cancers The relevant research results were published in the Journal of Science Translational Medicine on March 9, 2016, and the title of the paper was "development of a proposed derived thermal cyclic peptide that targets ovarian cancer via the more microenvironment" The first co authors of the paper are Dr summing Wang, Dr Anna Blois and Dr Tina El Rayes from the medical school of will Cornell, Boston Children's Hospital, USA; the corresponding authors of the paper are Dr Randolph watnick from Boston Children's hospital Picture from C Bickel / Science Translational Medicine Ovarian cancer is the fifth leading cause of cancer death in women, according to the American Cancer Society Before spreading, ovarian tumor is often silent in clinic As a result, many women with ovarian cancer are not diagnosed until they are in advanced stage Surgical resection and chemotherapy with paclitaxel and platinum anticancer drugs are the most common therapies, but ovarian cancer cells often develop resistance to these drugs, resulting in fewer treatment options for women with advanced ovarian cancer "Our goal is to develop treatments that treat patients without making them worse again," watnick said We want to find a way to treat cancer patients, but it doesn't depend on a mixture of cytotoxic drugs because they have obvious side effects " For the past 12 years, in order to achieve this goal, watnick laboratory has been trying to understand and manipulate the microenvironment in which tumors (especially metastatic tumors) grow and thrive In 2009, they announced that in breast and prostate cancer model animals, a protein called sphingolipid activating protein (PSAP) can block tumor metastasis PSAP promotes the production of thrombospondin-1 (TSP-1) by immune cells called monocytes TSP-1 is a powerful anti angiogenic and anti-inflammatory protein, which can make other tissues to resist tumor metastasis In 2013, in collaboration with LARS akslen, Ph.D., from Bergen University, Norway, and Vivek Mittal, Ph.D., from Weill Cornell Medical School, watnick confirmed that in prostate cancer, breast cancer and lung cancer model mice, as a five peptide fragment of PSAP, psaptide can trigger the generation of TSP-1 completely, and can significantly reduce the spread of metastasis In the current study, watnick, akslen and Mittal attempted to determine whether two modified versions of psaptide, d-psaptide and cyclopsaptide, could force metastatic tumor atrophy through TSP-1 D-psaptide is achieved by using right-handed amino acids (a mirror image of normal amino acids that the body cannot degrade so easily.) Obtained by replacing two amino acids in psaptide Cyclopsaptide is formed by cyclization of d-psaptide The researchers found that the ability of d-psaptide and cyclopsaptide to promote the release of TSP-1 increased three times and six times, respectively, compared with the natural psaptide, and they were more stable in human plasma The researchers tested the antitumor activity of the two modified peptides in a mouse model of ovarian cancer built from tumor cells from patients Ovarian cancer cells express a surface marker called CD36, which is also the receptor of TSP-1 When activated, it can promote ovarian cancer cells into apoptosis "It's important that we use these peptides as immunomodulators to turn monocytes into a transport vehicle to transport TSP-1 to ovarian tumors," explains watnick This strategy should not interfere with the immune response to specific tumor resistance " In the first group, mice were treated with cisplatin or d-psaptide for up to 83 days a day In the second group of experiments, these tumors were allowed to self-establish for a longer period of time, and then received cisplatin or cyclopsaptide treatment every day After a shorter period of time (15 days), any remaining tumors were carefully studied These experimental results are significant In the cisplatin / d-psaptide comparison, the tumor shrank in cisplatin treated mice about 20 days ago, but after that, the tumor developed resistance and began to grow again On the contrary, in mice treated with d-psaptide, the tumor shrank to an undetectable extent at 48 days, and remained so at the end of the experiment 35 days later In the cisplatin / cyclopsaptide comparison, at the end of 15 days of treatment, the metastatic tumors in mice treated with cyclopsaptide were 2.3 times smaller than those treated with cisplatin The researchers noted that TSP-1 was widely expressed in the tumor surrounding tissues in the mice treated with cyclophosphamide, whereas in the mice treated with cisplatin, TSP-1 was almost undetectable Finally, 59% of the tumor cells in the mice treated with cyclopsaptide were apoptotic, compared with 11% in the mice treated with cisplatin In summary, the data of this study provide a large number of strong evidence to support the further study of psaptide based drugs "In addition to ovarian cancer, many other tumors also express the receptor CD36 for TSP-1," watnick said It's a key receptor for tumor cell growth; if anything, it's when they become more aggressive, they express more CD36 We want to use this dependency against them " (Reprint) July 25, 2019