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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

FinancingSwitzerlandEU

29.04.2016 Swiss bank Group UBS has raised US$471m (€412m) for the UBS Oncology Impact Fund, which was set up to invest in early-stage cancer treatments. The money raised by the fund, nearly half of which comes from investors in Asia, is the largest amount ever raised for such a cancer investment fund.

Industry reportGermany

27.04.2016 More revenue, more jobs, more financing, more R&D expenditure – all signs point towards sustainable growth in the German biotech sector. These are the results of the most recent company survey 2016, published by biotechnologie.de. The report was once again conducted alongside the biotech standards defined by the organisation for economic cooperation and development (OECD).

Clinical ResearchFrancePortugal

21.04.2016 An expert panel’s final report on the fatal drug trial earlier this year in France states that the death of one of the participants was most likely caused by the drug’s toxicity and not by any violation of the rules.

Immuno-oncologyNetherlandsBelgium

21.04.2016 For up to US$685m (€606m), Dutch ArgenX has outlicensed its human antibody programme ARGX-115 to AbbVie. The pre-clinical immuno-oncology candidate targets a protein believed to contribute to immunosuppressive effects of T-cells.

RegulatorySwitzerlandEU

20.04.2016 The US government is forking out up to US$100m to get Basilea Pharmaceutica’s broad-spectrum antibiotic ceftobiprole on the US market. In the EU, ceftobiprole is already available.

Immuno-oncologyUK

19.04.2016 British drug developer Heptares Therapeutics and mAb maker Kymab Ltd have partnered up in yet another immuno-oncology collaboration. The companies plan to discover antibody meds targeting a superfamily of receptors.

FinancingSwitzerlandFranceEUGermanyDenmark

15.04.2016 Not every company is put off by the current stock market climate. Swiss biopharma company GeNeuro has gone public at Euronext Paris, raising €33m in the process. Others, meanwhile, have to find different ways to raise money.

Event ReviewSwitzerlandBelgiumEU

13.04.2016 Despite political disturbances, 2015 was a good year for the biotech scene in Switzerland. Net sales increased by 5.1% to CHF5,133m and 400 additional people found jobs in the sector. As usual, the new numbers were presented at the annual Swiss Biotech Day – which set new records as well.

FinancingGermanyNetherlandsEU

12.04.2016 German-Dutch life science investment specialist Forbion Capital Partners has raised more than €180m for its venture capital fund Forbion Capital Fund III. Once more the money will primarily go to European start-ups.

Event ReviewGermanyEU

08.04.2016 Do you win by being innovative?, was the question asked at this year’s DIA Euromeeting in Hamburg. In a relaxed and cooperative atmosphere, regulators, physicians and patients had ample opportunity to interact with the healthcare industry.

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