Improved effectiveness of chemotherapy for cancer

August 15, 2013, University of Bern
So-called «mitotic catastrophe» of a tumour cell: The image shows that the tumour cell is no longer able to divide after chemotherapy. However, the chromosomes (red) are distributed unequally. If this damaged cell does not die, it can cause cancer again. The group of scientists gathered by Hans-Uwe Simon discovered how cell death can be triggered and this cancer risk prevented. Credit: Hans-Uwe Simon, Institute of Pharmacology, University of Bern

Cancer cells often develop defence mechanisms which enable them to survive chemotherapy. A group of researchers from the Institutes of Pharmacology and Pathology in Bern present new solutions for preventing the development of such resistances.

Cells can break down damaged molecules as well as whole areas of the cells themselves by means of self-digestion and utilize the resulting from this process for the production of energy and new molecules or cell parts. This process of self-digestion is called autophagy and can be considered a renovation of the cell. The generation of energy by means of autophagy plays a special role for the cells if they do not have enough nutrients, oxygen or .

However, autophagy can also be used by in order to survive stress situations such as chemotherapy - they digest the destroyed cell parts and regenerate themselves. This makes them resistant to the therapy. Now, a group of scientists from the University of Bern under the direction of Hans-Uwe Simon from the Institute of Pharmacology has discovered that the autophagy of tumour cells can be influenced with pharmacological means. The findings reveal new therapy approaches for the . The study is published today in Nature Communications.

Preventing the 'reanimation' of tumour cells

The researchers studied the importance of autophagy for tumour cells. Often, chemotherapy alone is not able to destroy all of the tumour cells. While some of the tumour cells survive the therapy by means of autophagy, others go through a so-called "mitotic catastrophe", a state in which they are no longer able to divide. If these damaged cells do not die, they can cause cancer again.

Now, however, the group of scientists gathered by Hans-Uwe Simon has found a way to prevent the survival of cancer cells after chemotherapy. They discovered a connection between autophagy and mitotic catastrophe: when the self-digestion of cancer cells was suppressed by means of pharmaceuticals, the mitotic catastrophe directly resulted in cell death. This way, the survival mechanisms of were eliminated.

With this method, the effectiveness of the usual can be significantly improved: "We hope that, based on these findings, we will be able to develop new therapies which will prevent the chemoresistance of established tumours", said Hans-Uwe Simon, the head of the study.

Explore further: Neuroblastoma: Autophagy protects from chemotherapy

More information: Maskey, D. et al. ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy, Nature Communications, 15. August 2013. DOI: 10.1038/ncomms3130

Related Stories

Neuroblastoma: Autophagy protects from chemotherapy

July 1, 2013
Neuroblastomas are pediatric tumors that originate from cells of the embryonic nervous system. The disease can take widely varying clinical courses that range from spontaneous regression to fatal outcomes. Highly aggressive ...

Autophagy-addicted breast cancers killed by anti-malaria drug, chloroquine

April 8, 2013
The process of autophagy cleans cells – they wrap up the bad stuff and then dispose of it. And so it stands to reason that inhibiting autophagy would make cancer cells less able to cleanse themselves of chemotherapy and ...

Possible predictive biomarker for patients who may respond to autophagy inhibitors

April 8, 2013
Autophagy, the process by which cells that are starved for food resort to chewing up their own damaged proteins and membranes and recycling them into fuel, has emerged as a key pathway that cancer cells use to survive in ...

Researchers study effect of chemotherapy combined with immunotherapy for advanced cancers

October 9, 2012
Researchers at Moffitt Cancer Center and colleagues at the University of South Florida and Tianjin Medical University Cancer Institute and Hospital in China have discovered that combining chemotherapy drugs and immunotherapy ...

Recommended for you

New approach attacks 'undruggable' cancers from the outside in

January 23, 2018
Cancer researchers have made great strides in developing targeted therapies that treat the specific genetic mutations underlying a patient's cancer. However, many of the most common cancer-causing genes are so central to ...

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

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.