Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Developing Cancer Drugs

Published: Wednesday, June 19, 2013
Last Updated: Wednesday, June 19, 2013
Bookmark and Share
Researchers find therapeutic potential in ‘undruggable’ target.

Harvard Stem Cell Institute (HSCI) researchers have identified in the most aggressive forms of cancer a gene known to regulate embryonic stem cell self-renewal, beginning a creative search for a drug that can block its activity.

The gene, SALL4, gives stem cells their ability to continue dividing as stem cells rather than becoming mature cells. Typically, cells only express SALL4 during embryonic development, but the gene is re-expressed in nearly all cases of acute myeloid leukemia and 10 to 30 percent of liver, lung, gastric, ovarian, endometrial, and breast cancers, strongly suggesting it plays a role in tumor formation.

In work published in the New England Journal of Medicine, two HSCI-affiliated labs — one in Singapore and the other in Boston — show that knocking out the SALL4 gene in mouse liver tumors, or interfering with the activity of its protein product with a small inhibitor, treats the cancer.

“Our paper is about liver cancer, but it is likely true about lung cancer, breast cancer, ovarian cancer, many, many cancers,” said HSCI Blood Diseases Program leader Daniel Tenen, who also heads a laboratory at the Cancer Science Institute of Singapore (CSI Singapore). “SALL4 is a marker, so if we had a small molecule drug blocking SALL4 function, we could also predict which patients would be responsive.”

Studying the therapeutic potential of a transcription factor is unusual in the field of cancer research. Transcription factors are typically avoided because of the difficulty of developing drugs that safely interfere with genetic targets. Most cancer researchers focus their attention on kinases.

The HSCI researchers’ inquiry into the basic biology of the SALL4 gene, however, revealed another way to interfere with its activity in cancer cells. The gene’s protein product is responsible for turning off a tumor-suppressor gene, causing the cell to divide uncontrollably. Using this knowledge, the researchers demonstrated that targeting the SALL4 protein with druglike molecules could halt tumor growth. “The pharmaceutical companies decided that if it is not a kinase and it is not a cell surface molecule, then it is ‘undruggable,’ ” Tenen said. “To me, if you say anything is ‘undoable,’ you are limiting yourself as a biomedical scientist.”

Earlier this year, Tenen’s co-author, HSCI-affiliated faculty member Li Chai, a Harvard Medical School assistant professor of pathology at Brigham and Women’s Hospital, published a paper in the journal Blood, reporting that a SALL4 inhibitor has similar treatment potential in leukemia cells.

Chai took blood samples from patients with acute myeloid leukemia, treated the leukemic cells with the inhibitor that interferes with SALL4 protein activity, and then transplanted the blood into mice. The result was a gradual regression of the same cancer in mice.

“I am excited about being on the front line of this new drug development,” Chai said. “As a physician-scientist, if I can find a new class of drug that has very low toxicity to normal tissues, my patients can have a better quality of life.”

Chai and Tenen are now working with HSCI Executive Committee member Lee Rubin, the Harvard Institute of Chemistry and Cell Biology, and James Bradner of Dana-Farber Cancer Institute, another HSCI-affiliated faculty member, to overcome the technical challenges of drug development and demonstrate the potential of SALL4 interference to treat other forms of cancer.

“I think as academics, we seek to engage drug companies because they can do these types of things better than we can,” Tenen said. “But, also as an academic, I want to go after the important biologic targets that are not being sought after by the typical drug company — because if we do not, who will?”

The basic research that explored the biology of SALL4 was financed by a 2007 seed grant from HSCI, with more recent funding provided by a Singapore Translational Research Award from the Singapore National Medical Research Council, and grants from the Singapore Ministry of Education and National Research Foundation, and the National Institutes of Health. Kol Jia Yong, Chong Gao, and Henry Yang, among others, contributed to this work.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More Than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

A Cancer’s Surprise Origins, Caught in Action
First demonstration of a melanoma arising from a single cell.
Monday, February 01, 2016
Seeing Hope
Gene therapy/drug combo restores some vision in mice with optic nerve injury.
Wednesday, January 20, 2016
Diagnosing Cancer from a Single Drop of Blood
What if a physician could effectively diagnose cancer from one drop of a patient’s blood?
Friday, January 08, 2016
Detecting When and Why Deadly Blood Clots Form
New bioinspired blood coagulation assay is more sensitive than existing assays and could one day be used to diagnose rare bleeding disorders and prevent toxic effects of anticoagulant and antiplatelet drugs.
Wednesday, January 06, 2016
Helping Cells Forget Who They Are
Erasing a cell’s memory makes it easier to manipulate them into becoming another type of cell.
Wednesday, December 23, 2015
Gut-on-a-Chip Model Offers Hope for IBD Sufferers
Wyss Institute replicates gut’s microenvironment in the lab, allowing researchers new access.
Thursday, December 17, 2015
Cell Memory Loss Enables the Production of Stem Cells
Scientists identify a molecular key that helps maintain identity and prevents the conversion of adult cells into iPS cells.
Thursday, December 17, 2015
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
Tuesday, November 24, 2015
On Top of the Flu
Chance for advance warning in search-based tracking method.
Thursday, November 12, 2015
Escape Prevention
Studying flu virus structure brings us a step closer to a permanent vaccine.
Monday, October 05, 2015
Inroads Against Leukaemia
Potential for halting disease in molecule isolated from sea sponges.
Thursday, October 01, 2015
Exposure to Pesticides In Childhood Linked to Cancer
Young children who are exposed to insecticides inside their homes may be slightly more at risk for developing leukemia or lymphoma during childhood, according to a meta-analysis by Harvard T.H. Chan School of Public Health researchers.
Thursday, September 24, 2015
Genetic Sleuthing
Sabeti team applies Ebola methods to shed light on spread of Lassa fever.
Thursday, September 17, 2015
Why MS Symptoms May Improve As Days Get Shorter
New research from Brigham and Women’s Hospital offers an answer to ‘seasonal paradox’.
Monday, September 14, 2015
So Long, Snout
Research helps answer how birds got their beaks.
Thursday, August 20, 2015
Scientific News
Head Injury Patients have Protein Clumps Associated with Alzheimer’s Disease
Scientists have revealed that protein clumps associated with Alzheimer's disease are also found in the brains of people who have had a head injury.
Exposure to Air Pollution 30 Years Ago Associated with Increased Risk of Death
Exposure to air pollution more than 30 years ago may still affect an individual's mortality risk today, according to new research from Imperial College London.
More Then 1 in 20 U.S. Children have Dizziness and Balance Problems
Researchers at NIH have found that girls have a higher prevalence of dizziness and balance problems compared to boys, 5.7 percent and 5.0 percent.
Biosensors on Demand
New strategy results in custom "designer proteins" for sensing a variety of molecules.
Low-Cost, Portable NQR Spectroscopy
A researcher at Case Western Reserve University is developing a low-cost, portable prototype designed to detect tainted medicines and food supplements that otherwise can make their way to consumers. The technology can authenticate good medicines and supplements.
Structure of Brain Plaques in Huntington's
Researchers at the University of Pittsburgh School of Medicine have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder.
Insights into the Function of the Main Class of Drug Targets
About thirty percent of all medical drugs such as beta-blockers or antidepressants interact with certain types of cell surface proteins called G protein coupled receptors.
Spero Therapeutics Announces $30 Million Series B Preferred Financing
Company has announced financing of $30 million to support development of novel therapies to treat gram-negative bacterial infections.
Unique Mechanism for a High-Risk Leukemia
Researchers uncovered the aberrant mechanism underlying a notoriously treatment-resistant acute lymphoblastic leukemia subtype; findings offer lessons for understanding all cancers.
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!