Discovery could lead to targeted treatment for small-cell lung cancer

In collaboration with the Press Association

US researchers have discovered two molecules inside cells that may be important in the development of ‘small cell’ lung cancer (SCLC).

The lab-based research could be a first step towards new targeted treatments for this hard-to-treat disease, according to the scientists.

Small-cell lung cancers account for about eighteen out of every 100 cases of lung cancer.

The study, published in the journal Cancer Discovery, looked at differences between small cell cancer cells and non-small cell lung cancer (NSCLC) cells.

The results showed the molecules PARP1 and EZH2 – both types of protein – were present at significantly higher levels in SCLC cells.

Although people with SCLC initially respond to chemotherapy, the disease can often come back, according to study researcher Dr Lauren Byers, from the University of Texas.

The only currently approved treatments for SCLC are older chemotherapies, whereas newer-generation targeted drugs have been developed for NSCLC.

“Because most targeted therapies directly act on proteins, identifying if certain proteins are over-expressed in SCLC could have therapeutic applications,” Byers said.

Professor Siow-Ming Lee, Cancer Research UK's lung cancer expert based at the University College London Cancer Institute and Hospitals, said the work was at an early stage but was noteworthy, as there has been little change in treatment of SCLC over the past 20 years.

“This lab work suggests that clinical studies using treatments to block the proteins PARP and EZH2, together with chemotherapy, warrant further investigation. Scientists have already developed drugs that block PARP, which have shown some promise in treating breast and ovarian cancers – it will be interesting to see if these benefits extend to SCLC too," he added.

To identify the molecular differences, Byers and her colleagues examined the levels of about 200 proteins that are known to be involved in driving cancer growth.

“We discovered that SCLC and NSCLC have dramatically different protein profiles in terms of which proteins are ‘turned on’ and are driving the behaviour of these cancers,” Byers said.

“In small cell lung cancer, proteins that were present at higher levels included several DNA repair proteins such as PARP1 and a protein involved in cancer stem cell renewal, EZH2.”

According to Byers, the results show that, as with many targeted drugs, it is possible that combining PARP inhibitors with other drugs may significantly improve treatment.

References

  • Byers LA et al, Proteomic Profiling Identifies Dysregulated Pathways in Small Cell Lung Cancer and Novel Therapeutic Targets Including PARP1, Cancer Discovery (2012) DOI: 10.1158/2159-8290.CD-12-0112