News

Double strike against cancer
Enlarge image

ResearchGermany

Double strike against cancer

13.06.2013 - German researchers have found a way to circumvent chemotherapy resistance in cancer cells.

A new therapeutic approach can take advantage of cancer cells' need to repair double-strand breaks in DNA, in order to overcome the tumour's resistance to chemotherapy (Science Transl. Medicine). According to the research group headed by Hans Christian from University Cologne, mutations in the ATM gene protect cancer cells from cell death during chemotherapy. ATM  is instrumental in initiating DNA repair and inducing cell death when repair is not possible in curse of the so-called DNA damage response (DDR).  

But now the researchers have found that the protection offered by ATM mutations comes at a cost – dependence on a DNA-repairing enzyme called DNA-PKcs (DNAdependent protein kinase catalytic subunit). In experiments with mouse and human cancer cells, Christian et al. proved that it's possible to exploit this weak spot to fight blood cancer and solid tumours. Treating the cells with drugs that block DNA-PKcs led to cancer cell death. Intriguingly, both healthy cells and cancer cells with normal ATM function can tolerate the loss of DNA-PKcs, suggesting few side effects. The findings hint that drugs designed to specifically kill ATM-deficient tumours could benefit cancer patients.   The dependence of ATM-defective cells on DNA-PKcs offers a window of opportunity for therapeutic intervention: Either pharmacological or genetic abrogation of DNAPKcs in ATM-defective cells led to the accumulation of DNA double-strand breaks and the subsequent CtBP-interactingprotein (CtIP)-dependent generation of large single-stranded DNA (ssDNA) repair intermediates. These ssDNA structures trigger proapoptotic signalling through the RPA/ATRIP/ATR/Chk1/p53/Puma axis, ultimately leading to the apoptotic demise of ATM-defective cells exposed to DNA-PKcs inhibitors such as Celgene Corp.'s compound CC115. According to the researchers, such DNA-PKcs inhibitors are effective as single agents against ATM-defective lymphomas in vivo. CC-115 binds to and inhibits the activity of DNA-PK (DNA-dependent protein kinase) and both raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2), which may lead to a reduction in cellular proliferation of cancer cells expressing DNA-PK and TOR.  

Christian told EuroBiotechNews that his group currently is in negotiation with Celgene which is currently in Phase I testing of CC115. "We would like to extend the trial to a ATM-stratified population of CCL patients," he said. ATM is overexpressed in 10% of blood cancers and 10% of carcinomas of the lungs, colon, and pancreas.

© eurobiotechnews.eu/tg

http://www.european-biotechnology-news.com/news/news/2013-02/double-strike-against-cancer.html

AntibodiesDenmarkNetherlands

22.05.2015 Dutch arGEN-X and Danish LEO Pharma are pairing up to develop antibody-based treatments for the chronic inflammation that causes many skin conditions.

M&ANetherlandsGermanyEU

12.05.2015 US pharma is coming to European biotech to fill their pipeline. Pfizer is paying €77.5m for an option on Dutch AM-Pharma, while Juno Therapeutics acquired German biotech Stage Cell Therapeutics for around €72m.

Rare diseasesItalyGermanyPoland

15.05.2015 Rome-based pharmaceutical group Sigma-Tau has sold its blood cancer drug programme Oncaspar to US company Baxter, who aims to spin out its biopharma business.



BiologicsFinlandNetherlandsEU

26.05.2015 The Finnish Medicines Agency Fimea has joined the Dutch MEB in its stance on the interchangeability of biosimilars. The Fimea now sees physician-driven switching of biologics as unproblematic.

SurveyGermany

06.05.2015 More revenue, more staff, more funding: in the German biotech industry, all signs are pointing towards growth.

M&AUKSweden

18.05.2015 Double deal for allergy: UK’s speciality biopharma Circassia is boosting its asthma pipeline with the acquisition of Swedish asthma specialist Aerocrine as well as fellow British Prosonix.

FinancingUK

20.05.2015 The Scottish Government has announced it will double the amount of funds for rare diseases. The New Medicines Fund that was created last year for this purpose will be increased to £80m (€112m).

M&ASwitzerland

04.05.2015 Swiss crop chemical maker Syngenta AG is in talks with US company Monsanto to discuss a possible merger, insiders say.

BiofuelsEU

30.04.2015 The European Parliament has given the go-ahead on a new law limiting the use of harmful crop-based biofuel in the transport sector. The decision marks a breakthrough in the EU’s approach to biofuels.

Events

All Events

Partner-Events

Frankfurt am Main (DE)

ACHEMA 2015

Current issue

All issues

Product of the week

Products

Stock list

All quotes

TOP

  • MAGFORCE6.55 EUR9.17%
  • WILEX4.29 EUR5.41%
  • VITA 345.75 EUR1.77%

FLOP

  • EPIGENOMICS5.51 EUR-3.67%
  • BASILEA126.80 CHF-3.43%
  • BAYER129.15 EUR-3.19%

TOP

  • SYNGENTA425.50 CHF35.3%
  • EVOLVA1.79 CHF13.3%
  • BASILEA126.80 CHF13.1%

FLOP

  • CYTOS0.64 CHF-36.6%
  • MEDIGENE8.30 EUR-24.3%
  • THERAMETRICS0.07 CHF-12.5%

TOP

  • WILEX4.29 EUR436.2%
  • SANTHERA90.35 CHF330.2%
  • FORMYCON29.00 EUR322.7%

FLOP

  • MOLOGEN4.93 EUR-53.7%
  • BIOFRONTERA2.25 EUR-26.9%
  • PAION2.54 EUR-26.8%

No liability assumed, Date: 29.05.2015