Small cell lung cancer: new approach to overcoming chemo-resistance

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(c) 2023_Kateryna_KonShutterstock
(c) 2023_Kateryna_KonShutterstock

Small cell lung cancer accounts for about 15 percent of all diagnosed lung cancers and is still associated with a high mortality rate. SCLC tumours often develop resistance to chemotherapy and thus poor prognosis is due to tumour recurrence which occurs within only five to 14 months after initial diagnosis. As a recent research study led by Balazs Dme and Karin Schelch from MedUni Vienna shows, resistant cell lines can be successfully fought with a combination of two already available therapeutic agents. The study results were published in the medical journal "Clinical Cancer Research" and offer a promising approach for the development of new therapies for this particularly aggressive type of tumour.

The study follows on from earlier, highly regarded findings by the research group led by Balazs Dme 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, Ildik Kovcs, Christian Lang, Zsolt Megyesfalvi, Franziska Ferk, Miroslav Mik, Konrad Hoetzenecker, Clemens Aigner, Christian R. Kowol, Siegfried Knasmueller, Michael Grusch, Beta Szeitz, Melinda Rezeli, Balazs Dome, Karin Schelch
https://doi.org/10.1158/1­078-0432.C­CR-23-1795