Cancer drug stimulates tripolar mode of mitosis

September 12, 2017, Helmholtz Association of German Research Centres
Taxanes induce tripolar instead of normal bipolar cell division. The daughter cells are more sensitive to radiation damage. DNA is stained in blue, tubulin in red and centrosomes in green. Credit: Munich University Hospital

Taxanes inhibit cell division and make cancer cells sensitive to radiation therapy. A current study has investigated the underlying mechanisms of this action - and which biomarkers may be useful for predicting the success of therapy. The study, published in the journal Oncogene, was carried out within the framework of the Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer at Helmholtz Zentrum München and Munich University Hospital.

Taxane-based radiochemotherapy is widely used in the treatment of various locally advanced cancers - including non-small-cell lung carcinoma (NSCLC). Taxanes have two effects: they inhibit cell division, and they also sensitize tumor cells for . Researchers at the Department of Radiation Therapy & Radiooncology at Munich University Hospital and the Radiation Cytogenetics Research Unit at Helmholtz Zentrum München have now demonstrated in detail how this works.

Specifically, the scientists investigated the effect of Paclitaxel, a member of the taxane family isolated from the bark of the Pacific yew (Taxus brevifolia). "By using cell biological and biochemical approaches, we were able to show in the present study that clinically relevant doses of Paclitaxel induce tripolar instead of normal bipolar cell division," said first author Dr. Michael Orth of Munich University Hospital. Put in simple terms, instead of dividing into two cells, the cell divides into three. "Tumor cells that have undergone such cell division subsequently respond particularly well to radiation therapy."

Biomarkers could predict therapy success

However, the scientists found that not all perform the taxane-mediated tripolar cell division and thus are sensitized to . "The cells that respond are primarily that contain higher levels of the protein kinase AURKA and its cofactor TPX2," said Professor Kirsten Lauber of Munich University Hospital. Both molecules are involved in .

"We were also able to confirm the clinical relevance in a publicly accessible data set of 114 lung cancer patients," said Dr. Kristian Unger, deputy head of the Radiation Cytogenetics Research Unit at Helmholtz Zentrum München. "Patients with particularly high expression levels of AURKA and TPX2 in the tumor had significantly longer overall survival times when treated with taxane-based radiochemotherapy."

Accordingly, the scientists hope that they will be able to use the two molecules as biomarkers in the future in order to identify patients who can particularly benefit from taxane-based radiochemotherapy as well as patients for whom other options need to be chosen.

Co-author Professor Claus Belka, Director of the Clinic and Policlinic for Radiation Therapy and Radiation Oncology of Munich University Hospital and member of the German Consortium for Translational Cancer Research (DKTK), summarized the perspectives: "The present study identifies AURKA and TPX2 as the first mechanism-derived biomarkers of taxane-based radiochemotherapy. This is an important prerequisite for personalized decisions." In the future, the scientists want to further investigate the molecules and examine their capacity as predictive biomarkers of taxane-based radiochemotherapy.

Explore further: microRNAs help to predict disease progression in brain tumors

More information: M Orth et al, Taxane-mediated radiosensitization derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX2, Oncogene (2017). DOI: 10.1038/onc.2017.304

Related Stories

microRNAs help to predict disease progression in brain tumors

June 14, 2016
Scientists at the Helmholtz Zentrum München and the Ludwig Maximilians University of Munich (LMU) have developed a new method of predicting disease progression in gliobastoma patients who have undergone standard treatment. ...

New approach in T-cell therapy to treat cancer

June 8, 2017
Scientists have armed immune cells with a new surface molecule. This causes the cells to respond particularly aggressively when they encounter a protein that tumors actually use to camouflage themselves from the immune system. ...

Team improves radiation therapy for head and neck patients

May 31, 2017
Radiation therapy is one of the most common treatments used to fight cancer, with an estimated 500,000 people each year receiving radiation therapy either alone or in combination with other treatments. Patients are often ...

Researchers reveal underlying mechanism of powerful chemotherapy for prostate cancer treatment

September 17, 2012
The power of taxane-based chemotherapy drugs are misunderstood and potentially underestimated, according to researchers at Weill Cornell Medical College in the September 15 issue of the journal Cancer Research.

Combined radiotherapy and immunotherapy improve efficacy in a murine lung cancer model

June 16, 2016
Radiation therapy is commonly used to reduce tumor size and improve symptoms of non-small cell lung cancer. While initially beneficial, many patients will eventually relapse with metastatic tumors. Last year, two immunotherapies ...

Biomarker reveals cause of thyroid carcinoma

October 7, 2014
The expression of the protein CLIP2 provides information on whether a papillary thyroid carcinoma was induced by radiation or had a sporadic origin. With this discovery, scientists from the Helmholtz Zentrum München have ...

Recommended for you

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

Catching up to brain cancer: Researchers develop accurate model of how aggressive cancer cells move and spread

February 15, 2018
A brief chat at a Faculty Senate meeting put two University of Delaware researchers onto an idea that could be of great value to cancer researchers.

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.