预约演示

'One-two punch' of epigenetic cancer drugs could knock out colorectal cancer cells

2024-04-01

交易

上市批准免疫疗法临床研究

An upcoming trial in patients with colorectal cancer will be the first to test an DNMT inhibitor and an EZH2 inhibitor together in any type of cancer.

A pair of epigenetic cancer drugs pcolorectal cancerunch” against colorectal tumorDNMT knock them out moEZH2 inhibitor EZH2ffectively than either medication acancera new study in cells suggests.

In a journal article cancerhed March 27 in Science Advances, a teacolorectal tumorsled by scientists from the Van Andel Institute in Grand Rapids, Michigan showed that a low dose of the DNA methyltransferase (DNMT) inhibitor decitabine combined with Tithe EZH2 inhibitor tazemetostat successfully induced changes that would make cancer cells more vulnerable to destruction by the immune system. The chemotherapy decitabine is commercialized by Eisai as Inqovi; tazemetostat is commercialized by Ipsen as Tazverik. Neither company was involved in the study.

While agents in both classes of drugs are FDA approved to treat blood cancer, they haven't had much success inVan Andel Instituteas colorectal cancer, Scott Rothbart, Ph.D., the study’s corresponding author, said in a press rdecitabineur findings highlight the promise oftazemetostat cancer therapies by revealing how these two mcancerions interact, with the DNMT inhibitor priming cancer cells in a way that makdecitabine2 inhibitor more effecEisai”Inqovi tazemetostat Ipsen Tazverik

“Epigenetic” is a term that refers to typically reversible modifblood cancere to genes that do not directly altsolid tumors themselvcolorectal cancerfect their expression. Cancer progression involves many epigenetic changes both to the cancer cells themselves and to the immune cells cancerould otherwise destroy them.DNMT cancer EZH2 inhibitor EZH2

Scientists have attempted to destroy cancer by countering these changes pharmacologically and restoring the expression of anti-cancer genes. The most established means of dCancero is with histone deacetylase inhibitors, or HDAC inhibitocancerch as Merck’s Zolinza (vorinostat) for lymphoma and Acrotech Biopharma’s Beleodaq (belinostat) for myeloma. The only other FDA-approved DNMT inhibitor besides Inquovi is Celgene’s acute myeloid leukemia drug Vidaza (azacitidine). Tazverik is the sole EZH2 inhibitor with FDA approval.

Earlier work by Van Andel Institute rcancerhers showed that DNMT inhibitors cause cancer cells to act as though they’ve been incancer by a virus, making them more vulnerable to one’s immunhistone deacetylase inhibitors histone deacetylaseew study, the reHDAC inhibitors HDACchers hypothesized thMerckcauZolinza (vorinostat)lter lymphomas in Acrotech BiopharmaakeBeleodaq (belinostat) effemyelomathey would work better togetheDNMTan separately.Celgene acute myeloid leukemia Vidaza azacitidine Tazverik EZH2 inhibitor EZH2

To see whether tVan Andel Institutehe researchers started byDNMT inhibitors DNMTting them against cancerent types of colorectal cancer cells on their own, then looked at them in combination. The results backed up their rationale: EZH2 inhibitors compounded the changes initiaDNMT inhibitors DNMTby the DNMT inhibitors, boosting the duo’s effectivenEZH2 inhibitors EZH2

The findings are the basis for an upcoming clinical trial that will evaluate the pair against coloreccolorectal cancerients. Combinations of DNMT inhibitors and HDAC inhibitors have been tested in clinical trials tEZH2 inhibitors EZH2xed results, the study noted. The new trial will be DNMT inhibitors DNMTfirst to evaluate a DNMT inhibitor and an EZH2 inhibitor.

Future studies should evaluate the pair with immunotherapies, too, Rothbart noted in the releacolorectal cancernce in preclinical models thatDNMT inhibitors DNMT viruslike changHDAC inhibitors HDAChe drugs make in the cells could lead to a better response to drugs that boost the immune system.DNMT EZH2 inhibitor EZH2

“These data suggest future directions for testing whether DAC and TAZ treatments might improve tumor response to immunomodulating agents,” the researchers wrote in the study.

更多内容，请访问原始网站

文中所述内容并不反映新药情报库及其所属公司任何意见及观点，如有版权侵扰或错误之处，请及时联系我们，我们会在24小时内配合处理。

机构