Pre-Clinical Study Finds New Compound Effective in Small Cell Lung Cancer

Pre-Clinical Study Finds New Compound Effective in Small Cell Lung Cancer

shutterstock_128141276A recent study published in Cancer Cell by researchers at the Dana-Farber Cancer Institute and the Massachusetts Institute of Technology revealed that small cell lung cancer cells are sensitive to an investigational agent that can inactivate part of the tumor survival mechanism.

Researchers observed that upon administration of THZ1 in mice models of small cell lung cancer, tumor volumes were significantly smaller when compared to controls, and no toxic side effects were verified.

Furthermore, the compound is already in development to be used in human clinical trials.

“Small cell lung cancer is a disease for which new treatments are desperately needed,” Kwok-Kin Wong, MD, PhD, co-senior author of the study and medical oncologist at Dana-Farber said in a news release. “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.”

Of all lung cancer cases, small cell lung cancer (SCLC) is responsible for about 10-15% of all the cases, transforming itself into the most aggressive form of this type of malignancy.

Even though there are many known genes that carry mutations in SCLC, there is no known driver of this type of tumor. As such, no good clinical targets exist for efficient drug therapies.

The research team analyzed tumor samples from SCLC mice models, finding one small molecule blocker that worked the best – THZ1. This compound was developed by Dana-Farber researchers and has the capacity to inhibit a protein known as cyclin-dependent kinase 7 (CDK7), which plays an important role in gene transcription.

The main question was, since transcription is common to all types of cells, why then was THZ1 effective in killing SCLC cells but did not damage healthy ones?

The team found the answer to be within small sections of genetic material, called super-enhancers, which can control over transcription in tumor cells.

THZ1 has the capacity to suppress some genes that are found within these regions, and are essential for the survival of SCLC, but not normal cells.

“We found that SCLC cells are ‘addicted’ to transcription in a way that normal cells are not,” Dr. Wong explained. “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 next challenge is to find the right therapeutic window to treat patients with derivatives from this compound, which will hopefully be revealed after thorough clinical trials.

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