About Careers Internship MedBlog Contact us

Small Cell Lung Tumors Shrink With a New Agent in Pre-Clinical Testing

by Himabindu Venkatakrishnan on December 9, 2014 at 1:24 PM
Font : A-A+

 Small Cell Lung Tumors Shrink With a New Agent in Pre-Clinical Testing

Small cell lung cancer has been seen to be vulnerable to an agent that disables part of tumor cells' basic survival machinery, report researchers at Dana-Farber Cancer Institute and the Massachusetts Institute of Technology. Small cell lung cancer is a disease for which no new drugs have been approved for many years. 

In a study published today in the journal Cancer Cell, the investigators found that the agent THZ1 caused human-like small cell lung tumors in mice to shrink significantly, with no apparent side effects. The compound is now being developed into a drug for testing in human patients in clinical trials. 


"Small cell lung cancer is a disease for which new treatments are desperately needed," said Kwok-Kin Wong, MD, PhD, co-senior author of the study and medical oncologist at Dana-Farber. "Patients generally respond well to initial chemotherapy, but the disease almost always returns. Less than 5 percent of patients are alive five years after being diagnosed with the disease." Small cell lung cancer (SCLC) accounts for 10-15 percent of lung cancer cases and is the most aggressive form of lung malignancy.

Although small cell lung tumors have many mutated genes, none of these is known to be a "driver" - a gene that actually spurs tumor growth - and none makes a good target for drug therapy. As a result, researchers have sought other strategies for attacking the disease. Dana-Farber researchers began with mice that had small cell lung tumors engineered to resemble those in humans.

Extracting tumor tissue from the animals, the researchers screened more than 1,000 small molecule blockers in the cell samples to see if any halted tumor cell growth. The one that worked best was THZ1, a compound designed by chemical biologists at Dana-Farber that inhibits a cell protein known as cyclin-dependent kinase 7 (CDK7). CDK7 is known to play a key role in gene transcription, the process by which genetic information stored in DNA is copied onto RNA.

Inhibiting CDK7, therefore, strikes at the basic machinery of transcription. But since transcription occurs in all cells, researchers explored why THZ1 is effective at killing SCLC cells but left healthy cells unharmed. The answer lies in sections of genetic material known as super-enhancers, long stretches of DNA that exert extensive control over transcription in tumor cells. The researchers found that THZ1 suppresses certain genes within these regions that SCLC cells depend on to survive and grow.

Because normal cells do not rely on super-enhancers to the same degree, they are largely unaffected by THZ1. "We found that SCLC cells are 'addicted' to transcription in a way that normal cells are not," Wong observed. "They appear to depend on short-lived transcripts - briefly existing RNA copies - that aren't as critical to normal cells. This explains why normal cells can tolerate a drug that targets the basic transcription mechanism while SCLC cells cannot." 

The key to the effectiveness of drugs derived from THZ1 will be finding the correct "therapeutic window" for patients - the dose and administration schedule that produces the greatest therapeutic effect while producing the fewest side effects, Wong continued. Clinical trials will help determine that window. 

Source: Eurekalert


Recommended Readings

Latest Research News

Is There a Cure for Malaria Through Targeting Biological Clocks?
Malaria parasites sync their molecular rhythms with the internal 24-hour clocks of their hosts, said researchers.
Good Evenings Recovery Leads to Better Work Days
A latest research suggests that the quality of a person's post-work recovery in the evening can impact their mood when they resume work the next day.
Link Between Sleep Apnea and Cognitive Decline
Researchers are working on new strategies and solutions for sleep apnea to ward off a range of health risks including cognitive decline.
Softening Stem Cells Enhances Hair Growth Potential
The scientists discovered that when the stem cells in the hair follicle are made softer, they have a higher chance of growing hair.
Potential New Strategy for Ischemic Stroke Discovered
A combinatorial therapy provided promising beneficial results among people with ischemic stroke.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close

Small Cell Lung Tumors Shrink With a New Agent in Pre-Clinical Testing Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests