Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
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 3,300+ scientific posters on ePosters
  • More than 4,900+ 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

Scaling Up Tissue Engineering
Wyss Institute has invented Bioprinting technique that creates thick 3D tissues composed of human stem cells and embedded vasculature, with potential applications in drug testing and regenerative medicine.
Tuesday, March 15, 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
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
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
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
Promising Stem Cell Therapy
Animal model of breast-to-brain cancer spread allows testing of therapeutic-cell approach.
Monday, April 27, 2015
Brains or Skin?
Researchers identify a vital protein that can determine head and brain development.
Tuesday, March 17, 2015
Keeping Embryonic Stem Cells in Suspended Animation
Research reveals new strategy to control cellular identity and fate.
Monday, October 27, 2014
Giant Leap Against Diabetes
Ability to produce embryonic stem cells will allow researchers to push faster toward cure.
Friday, October 10, 2014
Improving Cord Blood Transplants
Researchers have published initial results of a Phase Ib human clinical trial of a therapeutic that could improve the success of blood stem cell transplantation.
Tuesday, October 15, 2013
Stem Cell Researchers Produce New Model of Leukemia Development
Two former Stanford University postdoctoral fellowsnow have the answer to why patients with leukemia stop producing healthy blood cells.
Friday, August 02, 2013
Study uses Stem Cells to Study Variants of Parkinson’s Disease
Personalized medicine closer to reality.
Tuesday, July 17, 2012
Stem Cell Transplant that 'Rebuilds Brain Circuitry'
A brain transplant of stem cells has worked in mice in a breakthrough that signals new hope for conditions from autism to Parkinson’s disease.
Tuesday, November 29, 2011
Helping the Heart Help Itself
An article published in the latest edition of the journal Cell Stem Cell, describes how research by the Harvard Stem Cell Institute points to new use for stem cells.
Wednesday, April 13, 2011
Scientific News
Genetic Variability in Cell Bank Lots
Researchers working with cancer cells from the same cell bank acquired at the same time, found that the cells were genetically different.
Human Stem Cells to Rapidly Generate Bone, Heart Muscle
A new study shows that combining positive and negative signals can quickly and efficiently steer stem cells down complex developmental pathways to become specialized tissues that could be used in the clinic.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer.
New Mechanism of Tuberculosis Infection
Researchers have identified a new infection mechanism of tuberculosis that could lead to a new therapeutic angle.
Modelling ALS Requires ‘Aged’ Stem Cells
Research suggests engineered cells are too ‘young’ to accurately model ALS and should be 'aged' to speed progress toward finding potential treatments.
Protein Reinforces Growth of Damaged Muscles
Biologists have found a protein involved in stem cells that bolsters damaged muscle tissue growth - potential for muscle degeneration treatments.
Treating HIV with Cancer-Fighting Gene Shows Promise
A type of gene immunotherapy that has shown promising results against cancer could also be used against HIV.
'Antigen-Presenting Cell' Defends Against Cancer
Through advanced imaging, researchers have identified cells that encourages increases in immune system cancer defences.
Rapid Generation from Stem Cells
Researchers coax human stem cells to rapidly generate bone and heart muscle by directing stem cells down complex developmental pathways.
HIV Hides No Longer
Researchers are working to create proteins that clear HIV-infected cells in order to eliminate latent infection and dormancy.
Skyscraper Banner

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!