The study follows on from earlier, highly regarded findings by the research group led by Balazs Döme and Karin Schelch (Department of Thoracic Surgery at MedUni Vienna), according to which small cell lung cancer (SCLC) can be divided into subtypes that respond differently to chemotherapeutic agents and targeted drugs. In this context, histone deaceylase inhibitors (HDACi) have been shown to be effective in two SCLC subtypes (known as SCLC-A and SCLC-N). HDACi are drugs that have already been shown in trials to be effective in fighting cells of different tumour types and have now been further investigated for their use in SCLC.
Combination instead of single therapy
SCLC affects about 15 percent of lung cancer patients. This particularly aggressive tumour, which usually occurs in smokers, grows rapidly and has a high tendency to metastasise. About 70 per cent of advanced cases are fatal within a year. "The high mortality rate is due to the rapid and virtually inevitable recurrence of the disease, which is often accompanied by resistance to treatment," says principal investigator Karin Schelch, outlining the problem. HDACi in combination with standard chemotherapeutic agents turned out to be a possible solution during the studies. This significantly slowed down the growth of tumour cells that were resistant to individual therapy.
Mechanism of resistance deciphered
In further analyses, the molecular mechanism underlying therapy resistance was also revealed. The findings of the MedUni Vienna research group thus contribute significantly to a better understanding of the biology of SCLC, a disease in which promising progress in the development of therapeutic innovations has been decades in waiting. "Our findings can provide the basis for research into successful new therapies that are superior to the resistance mechanisms of SCLC," says first author Anna Solta, also from MedUni Vienna's Department of Thoracic Surgery, highlighting the study's high clinical relevance.
Publication: Clinical Cancer Research
Entinostat enhances the efficacy of chemotherapy in small cell lung cancer through S-phase arrest and decreased base excision repair
Anna Solta, Kristiina Boettiger, Ildikó Kovács, Christian Lang, Zsolt Megyesfalvi, Franziska Ferk, Miroslav Mišík, Konrad Hoetzenecker, Clemens Aigner, Christian R. Kowol, Siegfried Knasmueller, Michael Grusch, Beáta Szeitz, Melinda Rezeli, Balazs Dome, Karin Schelch