Cause of chemoresistance in small cell lung cancer discovered

July 18, 2017, Medical University of Vienna
Cause of chemoresistance in small cell lung cancer discovered. Credit: Medical University of Vienna

Approximately one year after successful treatment with cytotoxic chemotherapy and radiotherapy, patients with advanced Small Cell Lung Cancer (SCLC), which primarily affects heavy smokers, generally relapse with recurrence of tumours that are resistant to further chemotherapy. At this point, the affected patients usually only have a few months to live. The reason for this was hitherto unknown. Researchers at MedUni Vienna, led by Gerhard Hamilton (Department of Surgery), have now discovered that circulating tumour cells combine, making previously chemo-sensitive cells into chemo-resistant cell complexes.

"The circulating aggregate to protect themselves from chemotherapy – like a circle of covered wagons – thereby preventing any active agents from entering," says Hamilton, describing the process. These "aggregates" can comprise hundreds of thousands of cells, be up to 2 mm in diameter and be eight times more resistant to chemotherapy drugs – firstly because hypoxic conditions are created inside the aggregates and secondly because these tumour cells reduce growth and are therefore less sensitive. The results were recently published in the prestigious journal Scientific Reports from Nature Publishing Group.

These results were facilitated by the permanent cultivation of circulating tumour of patients with advanced SCLC in Vienna. This was the first time in the world that this had been done. The research group headed up by Hamilton and Robert Zeillinger (Molecular Oncology Group, Department of Obstetrics and Gynecology, MedUni Vienna) and Maximilian Hochmair (Otto-Wagner Hospital) successfully developed seven cell lines from blood samples and then analysed these in the laboratory.

"And so, after 30 years of uncertainty, we managed for the first time to identify the causes of chemo-resistance," explains Hamilton. The scientists now intend to conduct further studies to find out how to either prevent or destroy these cell aggregates. According to the MedUni Vienna expert, a highly promising approach is to break up the cell complexes using enzymes or inhibitors.

Lung cancer now leads the field when it comes to cancer-related mortality in women

Fifteen percent of people with have Small Cell Lung Cancer. By the time of diagnosis, SCLC has usually already formed metastases and surgery is no longer an option – the prognosis for those patients is therefore poor. Their prospects are even worse, if they have developed resistance to chemotherapy. "In such cases, patients usually only survive a few months," says Hamilton. "In view of the fact that cancer has now overtaken breast cancer as the commonest cause of death from cancer among women, that is alarming. Since 1972, the proportion of deaths among women due to lung has increased from 10 percent to 22 percent – a figure backed up by the latest results from Statistik Austria. Young people, in particular young women, who smoke should be aware of the high risk of developing SCLC, as well as other non-malignant diseases."

Explore further: Circulating small cell lung cancer cells successfully cultivated for the very first time

More information: Lukas Klameth et al. Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance, Scientific Reports (2017). DOI: 10.1038/s41598-017-05562-z

Related Stories

Circulating small cell lung cancer cells successfully cultivated for the very first time

November 19, 2015
Most cases of small cell lung cancer are only diagnosed after the tumour has already formed metastases. Until now it has not been possible to investigate the reasons for this rapid metastasis, because of a lack of sufficient ...

Newly discovered clues to the cause of chemoresistance in small cell lung cancer

April 4, 2016
Small cell lung cancer is not usually detected until it is at an advanced stage, when metastases have already formed. Chemotherapy is very effective initially but, within a year, cancer recurs and this time does not respond ...

Advanced radiotherapy improves lung cancer survival rates

July 4, 2017
A 10-year University of Manchester and Christie NHS Foundation Trust study which used advanced radiotherapy techniques in patients with limited-stage small cell lung cancer (SCLC) has achieved the best survival rates and ...

Blood test could predict best treatment for lung cancer

November 21, 2016
A blood test could predict how well small-cell lung cancer (SCLC) patients will respond to treatment, according to new research published in Nature Medicine today (Monday).

Protein biomarker as potential tool for predicting lung cancer survival

December 7, 2016
The biomarker PD-1, a protein, could potentially be used to predict survival or disease-free survival of lung cancer patients who have had the tumour surgically removed. This is substantiated by the results of a study conducted ...

Prognostic factor indicates risk of cancer recurrence following radical prostatectomy

June 27, 2016
Slightly more than 10% of all patients who undergo successful surgery for prostate cancer have an elevated risk of tumor recurrence afterwards – especially as metastases. Under the microscope, it is possible to identify ...

Recommended for you

Researchers decipher the genome in chronic lymphocytic leukaemia

May 23, 2018
A team of researchers from University of Barcelona (UB) and their collaborators report for the first time the complete epigenome of chronic lymphocytic leukaemia, the most common type of leukaemia. The study, published in ...

Scientists discover how breast cancer hibernates: study

May 22, 2018
Scientists have identified the mechanism that allows breast cancer cells to lie dormant in other parts of the body only to reemerge years later with lethal force, according to a study published Tuesday.

Researcher: Big data, networks identify cell signaling pathways in lung cancer

May 22, 2018
A team of scientists led by University of Montana cell biologist Mark Grimes has identified networks inside lung cancer cells that will help understand this cancer and fight it with drug treatments.

Resetting the epigenetic balance for cancer therapy

May 22, 2018
Though mutations in a gene called MLL3 are common across many types of cancers, their relationship to the development of the disease has been unclear. Now, a Northwestern Medicine study has identified an epigenetic imbalance ...

Downward-facing mouse: Stretching reduces tumor growth in mouse model of breast cancer

May 22, 2018
Many cancer patients seek out gentle, movement-based stretching techniques such as yoga, tai chi and qigong, but does stretching have an effect on cancer? While many animal studies have attempted to quantify the effects of ...

Compound in citrus oil could reduce dry mouth in head, neck cancer patients

May 21, 2018
A compound found in citrus oils could help alleviate dry mouth caused by radiation therapy in head and neck cancer patients, according to a new study by researchers at the Stanford University School of Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.