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

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
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 2,800+ scientific posters on ePosters
  • More Than 4,000+ 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 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

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
Asthma Cells Scramble Like ‘There’s a Fire Drill’
Movement offers insight into mechanisms of asthma, other diseases.
Friday, August 14, 2015
Delivering Hope in Ovarian Cancer
Gene therapy blocked chemoresistant tumor growth in mice.
Tuesday, August 11, 2015
Potential Treatment for Muscular Dystrophy
A new method for producing muscle cells could offer a better model for studying muscle diseases, such as muscular dystrophy, and for testing potential treatment options.
Wednesday, August 05, 2015
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Friday, July 31, 2015
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
Monday, July 27, 2015
Pesticide Found in 70 Percent of Massachusetts’ Honey Samples
New Harvard University study says that the pesticide commonly found in honey samples is implicated in Colony Collapse Disorder.
Monday, July 27, 2015
The Secrets of Secretion
Researchers have hacked nature's blueprints to create a new technology that could have broad-reaching impact on drug delivery systems and self-healing and anti-fouling materials.
Tuesday, June 23, 2015
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Kitchen Utensils Can Spread Bacteria Between Foods
In a recent study researchers found that produce that contained bacteria would contaminate other produce items through the continued use of knives or graters—the bacteria would latch on to the utensils commonly found in consumers' homes and spread to the next item.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Safer, Faster Way To Remove Pollutants From Water
Using nanoparticles filled with enzymes proves more effective than current methods.
Drug May Prevent Life-Threatening Muscle Loss in Advanced Cancers
New data describes how an experimental drug can stop life-threatening muscle wasting (cachexia) associated with advanced cancers and restore muscle health.
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Novel Tumor Treatment
In the first published results from a $386,000 National Cancer Institute grant awarded earlier this year, a paper by Scott Verbridge and Rafael Davalos has been published.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Chemical Design Made Easier
Rice University scientists prepare elusive organocatalysts for drug and fine chemical synthesis.
New Analysis Technique for Chiral Activity in Molecules
Professor Hyunwoo Kim of the Chemistry Department and his research team have developed a technique that can easily analyze the optical activity of charged compounds by using nuclear magnetic resonance (NMR) spectroscopy.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos