Feinberg
Northwestern Medicine | Northwestern University | Faculty Profiles

News Center

  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Releases
  • Media Coverage
  • Podcasts
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Menu
  • Categories
    • Campus News
    • Disease Discoveries
    • Clinical Breakthroughs
    • Education News
    • Scientific Advances
  • Press Releases
  • Media Coverage
  • Podcasts
  • Editor’s Picks
    • COVID-19
    • Cardiology
    • Cancer
    • Neurology and Neuroscience
    • Aging and Longevity
    • Artificial Intelligence in Medicine
  • News Archives
  • About Us
    • Media Contact
    • Share Your News
    • News Feeds
    • Social Media
    • Contact Us
Home » Combining Epigenetic and Metabolic Approaches for Targeted Cancer Treatment
Scientific Advances

Combining Epigenetic and Metabolic Approaches for Targeted Cancer Treatment

By Olivia DimmerJun 22, 2023
Share
Facebook Twitter Email

Northwestern Medicine scientists have identified a novel vulnerability in a subset of genes commonly mutated in cancer, according to a study recently published in The Journal of Clinical Investigation.

Mutations in a set of genes known as the COMplex of Proteins Associated with Set1 (COMPASS) family, specifically mutations in the genes MLL3 and MLL4, are common in patients with many types of cancer.

To better understand these genes and what role they play in tumor growth, investigators performed a CRISPR screen in embryonic stem cells from mice with both MLL3 and MLL4 deleted. The MLL3 and MLL4 knockout cells appeared to ramp up the production of purine, an essential building block for DNA and RNA, according to the study.

The scientists then treated the MLL3 and MLL4 deleted cells with a purine synthesis inhibitor, which hampered cell growth.

Ali Shilatifard, PhD, the Robert Francis Furchgott Professor and chair of Biochemistry and Molecular Genetics, was senior author of the study published in The Journal of Clinical Investigation.

To see if cancers with mutations in these genes could be slowed with a similar tactic, the investigators tested their approach on cells from patients with colorectal cancer, which commonly features mutations in MLL3 and/or MLL4. They found that cancer cells with mutations in MLL3/4 were more sensitive to the purine synthesis inhibitor as compared to cells expressing wild type MLL4, according to the study.

The findings could represent a potential treatment direction for different cancers that share MLL3 or MLL4 mutations, said Ali Shilatifard, PhD, the Robert Francis Furchgott Professor and chair of Biochemistry and Molecular Genetics and senior author of the study.

“MLL3 and MLL4 are highly mutated in a large number of solid tumors and hematopoietic malignancies. There’s very little therapy for these cancers and understanding what causes the cells to become cancerous as a result of this mutation is going to be central for the development of targeted therapeutics,” said Shilatifard, who is also the director of the Simpson Querrey Institute for Epigenetics and leader of the Cancer Epigenetics & Nuclear Dynamics Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Our work is showing that basically the purine metabolism inhibition is one way of treating the cells that have mutations for MLL4.”

Shilatifard said he hopes to move to preclinical studies to further validate the efficacy of the approach.

“A large number of tumors don’t respond to immunotherapy. We think that this mixture of immunotherapy with epigenetic therapy and metabolism therapy, that combination could be very powerful,” he said.

Zibo Zhao, PhD, research assistant professor of Biochemistry and Molecular Genetics, was first author of the study. Kaixiang Cao, PhD, a former postdoctoral fellow in Shilatifard’s lab, was also a co-author of the study.

“We hope our research can support the translation of this to clinical settings and then we could use this as a biomarker to stratify the patients, so they can get more personalized therapy by targeting these mutations in human cancer,” Zhao said.

Other Feinberg faculty co-authors included Feng Yue, PhD, the Duane and Susan Burnham Professor of Molecular Medicine; Navdeep Chandel, PhD, the David W. Cugell, MD, Professor of Medicine in the Division of Pulmonary and Critical Care and of Biochemistry and Molecular Genetics; Rintaro Hashizume, MD, PhD, research associate professor of Biochemistry and Molecular Genetics; and Issam Ben-Sahra, PhD, assistant professor of Biochemistry and Molecular Genetics. All are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The study was supported by National Institutes of Health grants R35-CA197569, K99HD094906 and R50-CA221848.

Biochemistry and Molecular Genetics Cancer Genetics Research
Share. Facebook Twitter Email

Related Posts

Mapping Neural Activity Patterns and Odor Perception  

Sep 28, 2023

Small, Implantable Device Could Sense and Treat Cancer

Sep 26, 2023

Gene Linked to Glioblastoma Stem Cell Self-Renewal and Immunosuppression

Sep 26, 2023

Comments are closed.

Latest News

Mapping Neural Activity Patterns and Odor Perception  

Sep 28, 2023

Lloyd-Jones Announces He is Stepping Down as Chair of Preventive Medicine

Sep 27, 2023

Small, Implantable Device Could Sense and Treat Cancer

Sep 26, 2023

Gene Linked to Glioblastoma Stem Cell Self-Renewal and Immunosuppression

Sep 26, 2023

Northwestern Simulation’s In Situ Training Tests Cardiac Arrest Response Teams

Sep 25, 2023
  • News Center Home
  • Categories
  • Press Release
  • Media Coverage
  • Editor’s Picks
  • News Archives
  • About Us
Flickr Photos
20230914_NM461
20230914_NM644
20230914_NM345
20230914_NM444
20230914_NM464
20230914_NM520
20230914_NM673
20230914_NM641
20230914_NM612
20230914_NM608
20230914_NM602
20230914_NM597

Northwestern University logo

Northwestern University Feinberg School of Medicine

RSS Facebook Twitter LinkedIn Flickr YouTube Instagram
Copyright © 2023 Northwestern University
  • Contact Northwestern University
  • Disclaimer
  • Campus Emergency Information
  • Policy Statements

Type above and press Enter to search. Press Esc to cancel.