Navigation Links
Novel approach scores first success against elusive cancer gene
Date:9/9/2011

Dana-Farber Cancer Institute scientists have successfully disrupted the function of a cancer gene involved in the formation of most human tumors by tampering with the gene's "on" switch and growth signals, rather than targeting the gene itself. The results, achieved in multiple myeloma cells, offer a promising strategy for treating not only myeloma but also many other cancer types driven by the gene MYC, the study authors say. Their findings are being published by the journal Cell on its website Sept. 1 and in its Sept. 16 print edition.

"Cancer is a disease of disregulation of growth genes in a cell, and MYC is a master regulator of these genes," says James E. Bradner, MD, of Dana-Farber, one of the study's senior authors. Previous attempts to shut down MYC by inhibiting it directly with drug molecules have been notably unsuccessful. "In this study, our idea was to switch MYC off, interfering with its ability to activate the cell-growth program."

They did so with a small molecule called JQ1, developed by Dana-Farber's Jun Qi, PhD, a co-author of the new study and namesake of JQ1. In multiple myeloma, MYC is hyperactive constantly ordering cells to grow and divide because it is in the wrong position in the cells' chromosomes. Instead of its normal, quiet neighborhood, MYC finds itself adjacent to a gene known as the immunoglobulin gene. This busy gene is switched on by bits of DNA known as immunoglobulin enhancers, which normally prompt the cell to begin producing disease-fighting antibodies. In myeloma, the immunoglobulin enhancers act on the out-of-place MYC gene like an impatient finger at a doorbell, repeatedly activating it.

Researchers found that the enhancers are loaded with a "bromodomain" protein called BRD4, which, they demonstrate, is used to switch on MYC. Conveniently, it is targeted by JQ1. When investigators added JQ1 to laboratory samples of myeloma cells, the bromodomain proteins fell off the enhancers and the enhancers abruptly stopped working. The result: a shutdown of MYC and a slowdown of cancer cell division.

"In a sense, the JQ1 molecule cuts the cable that activates MYC and also connects MYC to the cell-growth genes," Bradner says. "The signal is interrupted and growth abruptly stops."

When investigators administered JQ1 to laboratory mice harboring myeloma cells, the disease receded and the animals lived longer than those that had not been treated. The study authors emphasize that JQ1 is a protytpe drug and cannot be used immediately to treat myeloma or other cancers. Its success in the current study illuminates the promise of JQ1-based therapies that target bromodomain proteins in cancers dependent on MYC for their growth.

"Together, our findings show that BRD4 has an important role in maintaining MYC activity in myeloma and other blood-related malignancies," says the study's senior author, Constantine Mitsiades, MD, of Dana-Farber. "They also point to the potential usefulness of drug-like bromodomain inhibitors as novel therapies against these diseases."


'/>"/>

Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
Dana-Farber Cancer Institute
Source:Eurekalert

Related biology news :

1. Novel method for increasing antibiotic yields
2. Tropical coral could be used to create novel sunscreens for human use, say scientists
3. A novel mechanism that regulates pro-inflammatory cells is identified
4. Novel analysis by Allen Institute sheds new light on the mechanisms of brain development
5. Novel gene increases yeasts appetite for plant sugars
6. Life scientists use novel technique to produce genetic map for African Americans
7. Parkinsons Disease Foundation announces $1 million for novel studies into Parkinsons
8. UTHealth awarded FEMA grant to explore novel obesity risk factor among firefighters
9. Efficiency record for flexible CdTe solar cell due to novel polyimide film
10. New clinical trial to test novel approach to treat triple-negative breast cancer
11. Novel prodrug alleviates symptoms in Huntingtons and Alzheimers mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/13/2016)... , January 13, 2016 ... has published a new market report titled - Biometric Sensors ... and Forecast, 2015 - 2023. According to the report, the global ... and is anticipated to reach US$1,625.8 mn by 2023, ... 2023. In terms of volume, the biometric sensors market ...
(Date:1/11/2016)... Synaptics Incorporated (NASDAQ: SYNA ), the ... its ClearPad ® TouchView ™ 4300 touch ... categories in the 8 th Annual Mobile Excellence ... The Synaptics ® TDDI solution enables faster time-to-market, ... devices, brighter displays and borderless designs. ...
(Date:1/8/2016)... MANCHESTER, United Kingdom , Jan. 8, 2016 ... innovative sensor-based diagnostic products, today announced the closing of a ... existing investors.  Proceeds from the financing will be used to ... hand-held device for detecting early-stage pressure ulcers. ... after receiving CE Mark approval. The device,s introduction has ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Florida , February 11, 2016 ... PositiveID Corporation ("PositiveID" or "Company") (OTCQB: PSID), a ... announced today that its Thermomedics subsidiary, which markets ... on its growth plan in January 2016, including ... distributors, increasing sequential monthly sales growth, and establishing ...
(Date:2/10/2016)... /PRNewswire/ - BioAmber Inc. (NYSE: BIOA ), a ... Mitsui & Co. Ltd., its partner in the ... investing an additional CDN$25 million in the joint venture ... 30% to 40%.  Mitsui will also play a stronger ... Sarnia , providing dedicated resources alongside ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... that it has joined the Human Vaccines Project, a public-private partnership to ... cancer. , The Human Vaccines Project brings together leading pharmaceutical and ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... ... attend the International Society of Pharmaceutical Engineering (ISPE) Rocky Mountain Chapter 21st Annual ... is expecting to fill more than 100 tables for its annual event, which ...
Breaking Biology Technology: