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Targeted approach to therapy for rare type of bone cancer

09.04.2019

Chordomas are rare bone tumors for which only few options of treatment exist. Scientists and doctors from the National Center for Tumor Diseases (NCT) Heidelberg, the German Cancer Research Center (DKFZ), and Heidelberg University Hospital (UKHD) have discovered a particular genetic trait of chordomas in advanced stages after conducting gene analysis. Their findings, published in the journal Nature Communications, indicate that a group of drugs, which have already been approved for treating other types of cancer, could also be effective in treating chordomas.

Chordomas are rare tumors of the spinal column. They make up around one percent of all bone tumors. They are categorized as bone tumors; however, they do not develop in bone tissue but rather from remnants of the so-called chorda dorsalis, which is found on the end of the spine. Usually this tumor of the spinal column appears in patients after they reach 30 years of age, and it affects men and women equally.


Left: patient with advanced-stage chordoma; right: cessation of tumor growth after five months of treatment with a PARP inhibitor

Photo credits: NCT Heidelberg

Treatment is often difficult because chordomas are typically resistant to conventional chemotherapy. Doctors try to surgically remove the affected tissue, which is not always completely successful.

As a result, the majority of those affected must subsequently undergo radiotherapy. In about two thirds of cases, the tumor comes back again. Researchers are therefore looking for new ways and approaches to deal with this disease.

Scientists and doctors from NCT Heidelberg, DKFZ, and UKHD in cooperation with colleagues from the German Cancer Consortium (DKTK) have now completed a detailed gene analysis of tumor cells from chordoma patients. The project was part of the NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication) program.

The study headed by Stefan Fröhling, Managing Director of NCT Heidelberg, addresses especially young patients with advanced-stage cancers and patients with very rare tumors (www.nct-heidelberg.de/master).

Overall, the team examined eleven patients with chordomas in an advanced stage and who had already undergone a wide range of standard therapies. The scientists completely sequenced the genetic material in the cancer cells and discovered that advanced-stage chordomas exhibit certain molecular changes associated with an abnormal DNA repair via a process called homologous recombination (HR).

In general, cells use HR to repair damaged portions of DNA strands. It is well known that HR is impaired in other types of cancer cells. Certain conditions must be in place to correctly diagnose this incorrect function.

"However only three of the eleven patients studied showed these criteria," reports Stefan Gröschel, Attending Physician at UKHD and Head of the Research Group Molecular Leukemogenesis at DKFZ. "In chordomas, apparently other, hitherto unknown genetic changes lead to an impairment of HR."

As certain drugs have proven to be effective in other types of cancer that also demonstrate a lack of HR, they appeared as a good option for additional treatment of chordoma patients. The doctors conducted experimental treatment using a PARP inhibitor in an individual patient with the matching genetic profile. PARP inhibitors inhibit the enzyme poly-ADP ribose polymerase and prevent the cancer cells from repairing damage to their DNA, which may occur after chemotherapy. After administering a PARP inhibitor, the patient demonstrated a long-lasting clinical improvement, and the tumor stopped growing.

"Our results show how the search for new personalized cancer treatments can be applied in clinical practice." By administering an approved drug that had yet to be used to treat chordomas, we were able to improve the patient's condition over a period of ten months," reports Fröhling.

In addition, the team led by Fröhling, Gröschel, and Robert Russell from Bioquant Heidelberg was able to identify a new resistance mutation of the PARP1 enzyme, which counteracted the effect of the PARP inhibitor in the same patient after the disease once again showed signs of progression.

An image for the press release is available free of charge on the internet:
https://www.nct-heidelberg.de/fileadmin/media/nct-heidelberg/news/Meldungen/Bild...
Left: patient with advanced-stage chordoma; right: cessation of tumor growth after five months of treatment with a PARP inhibitor

Original publication:
Stefan Gröschel, Daniel Hübschmann, Francesco Raimondi, et al. (2019) Defective homologous recombination DNA repair as therapeutic target in advanced chordoma. Nature Communications, DOI: 10.1038/s41467-019-09633-9

Notice for image material in press releases The use of images is free of charge. The NCT Heidelberg permits one-time use in connection with coverage of the subject of the press release. Please list the photo credits: "NCT Heidelberg". The transmission of photographic material to third parties is only permitted after prior consultation with the NCT Press Office (phone 0049 (0)6221 56 5930, Email: friederike.fellenberg@nct-heidelberg.de). Use for commercial purposes is prohibited.

Press contact:
Dr. Friederike Fellenberg
National Center for Tumor Diseases Heidelberg (NCT) Press and Public Relations Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 56-5930
Fax: +49 6221 56-5350
Email: friederike.fellenberg@nct-heidelberg.de
www.nct-heidelberg.de

Dr. Sibylle Kohlstädt
German Cancer Research Center (DKFZ)
Communications and Marketing
Im Neuenheimer Feld 280
69120 Heidelberg
Tel.: +49 6221 42-2843
Fax: +49 6221 42-2968
Email: s.kohlstaedt@dkfz.de
www.dkfz.de

Doris Rübsam-Brodkorb
Heidelberg University Hospital and Medical Faculty of the University of Heidelberg Press and Public Relations Im Neuenheimer Feld 672
69120 Heidelberg
Tel.: +49 6221 56-5052
Fax: +49 6221 56-4544
Email: doris.ruebsam-brodkorb@med.uni-heidelberg.de
www.klinikum.uni-heidelberg.de

National Center for Tumor Diseases Heidelberg (NCT)

The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital (UKHD) and German Cancer Aid. The NCT's goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. This is true for both diagnosis and treatment, follow-up care or prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here, the patients benefit from an individual treatment plan prepared in interdisciplinary expert rounds, so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. Since 2015, the NCT Heidelberg has maintained a partner site in Dresden. The Hopp Children's Cancer Center (KiTZ) was established in Heidelberg in 2017. The pediatric oncologists at KiTZ work together in parallel structures with the NCT Heidelberg.

German Cancer Research Center (DKFZ)

The German Cancer Research Center (DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful.
The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Together with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic.
In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

Heidelberg University Hospital

Heidelberg University Hospital (UKHD) is one of the most important medical centers in Germany; Heidelberg University's Medical Faculty is one of Europe's most prestigious biomedical research facilities. Their shared objective is the development of innovative diagnostics and treatments and their prompt implementation for the benefit of the patient. The hospital and faculty employ approximately 13,000 individuals and are involved in training and qualification. Every year approximately 65,000 patients are treated as inpatients and 56,000 as day patients in more than 50 specialized clinical departments with around 2,000 beds, with more than 1 million patients being treated as outpatients. Together with the German Cancer Research Center and German Cancer Aid, the Heidelberg University Hospital established The National Center for Tumor Diseases (NCT) Heidelberg as the leading oncology center of excellence in Germany. The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical training in Germany. At present 3,700 aspiring physicians and doctors are studying in Heidelberg.

Wissenschaftliche Ansprechpartner:

Stefan Fröhling, Stefan Gröschel

Originalpublikation:

Stefan Gröschel, Daniel Hübschmann, Francesco Raimondi, et al. (2019) Defective homologous recombination DNA repair as therapeutic target in advanced chordoma. Nature Communications, DOI: 10.1038/s41467-019-09633-9

Weitere Informationen:

http://www.nct-heidelberg.de

Dr. Friederike Fellenberg | idw - Informationsdienst Wissenschaft

Further reports about: CANCER Centrum für Tumorerkrankungen DNA DNA repair PARP Tumor cancer cells homologous

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