Navigation Links
An article in 'Cell' reveals a new resistance mechanism to chemotherapy in breast and ovarian cancer

It is estimated that between 5% and 10% of breast and ovarian cancers are familial in origin, which is to say that these tumours are attributable to inherited mutations from the parents in genes such as BRCA1 or BRCA2. In patients with these mutations, PARP inhibitors, which are currently in clinical trials, have shown encouraging results that make them a new option for personalised cancer treatment, an alternative to standard chemotherapy. Nevertheless, the latest studies indicate that a fraction of these patients generate resistance to the drug and, therefore, stop responding to the new treatment.

The team led by Spanish National Cancer Research Centre researcher scar Fernndez-Capetillo, head of the Genomic Instability Group, together with researchers from the National Cancer Institute in the US, have participated in a study that describes the causes that explain why tumours with BRCA1 and BRCA2 mutations stop responding to PARP inhibitor drugs.

"PARP inhibitors are only toxic in tumours that have an impaired DNA repair mechanism, such as those that contain BRCA1/2 mutations" says Mara Nieto-Soler, a researcher from Fernndez-Capetillo's team.

According to the researchers, the problem arises when these tumours, in addition to having BRCA1 and/or BRCA2 mutations, also contain secondary mutations in other proteins such as 53BP1 or PTIP, whose function is to restrain DNA repair. In these cases, the mutations mutually compensate for each other, the tumour cells recover the ability to repair their DNA and the drug stops working.

Fernndez-Capetillo says: "This is one of the first studies to demonstrate that secondary mutations can make tumours resistant when faced with specific treatments like, in this case, PARP inhibitors".


When the researchers compared different treatments, they observed that for those tumours with BRCA1 and/or BRCA2 mutations that also presented mutations in 53BP1 or PTIP, standard treatment with cisplatin was more efficient than personalised therapy.

"These data indicate that only patients containing mutations in BRCA1 and/or BRCA2, but not in the secondary genes we have described, would be candidates for an effective personalised therapy with PARP inhibitors", explains Fernndez-Capetillo, concluding that: "Our results suggest that 53BP1 and PTIP genes would need to be evaluated in patients with familial breast and ovarian cancer when deficiencies in the BRCA genes were present before deciding on their treatment".

In this context, researchers intend to warn healthcare providers in personalised medicine that the challenge, in addition to the search for markers of drug sensitivity for new pharmacological compounds, also encompasses the search for secondary resistance markers. The aim would be to bring about significant improvements in treatment outcomes.


Contact: Press Office
Centro Nacional de Investigaciones Oncologicas (CNIO)

Related biology news :

1. 7 new GSA Bulletin articles posted online ahead of print
2. MU researchers develop radioactive nanoparticles that target cancer cells
3. GSAs top geoscience journal posts 9 new articles
4. Microscopic dust particles found in underground railways may pose health risk
5. Long-term exposure to fine particles of traffic pollution increases risk of heart disease
6. Ultrafine particles raise concerns about improved cookstoves
7. Transmission routes of spreading protein particles
8. Trackable drug-filled nanoparticles -- a potential weapon against cancer
9. Kauai, the Petrified Forest, Costa Rica, and more: New GSA Bulletin articles now online
10. PeerJ publishes its first articles
11. From grains of volcanic glass to continental rifting: New Geosphere articles now online
Post Your Comments:
(Date:11/17/2015)... Paris , qui ... Paris , qui s,est tenu du ... leader de l,innovation biométrique, a inventé le premier scanner ... sur la même surface de balayage. Jusqu,ici, deux scanners ... les empreintes digitales. Désormais, un seul scanner est en ...
(Date:11/12/2015)... , Nov. 12, 2015  A golden retriever ... Duchenne muscular dystrophy (DMD) has provided a new lead ... Children,s Hospital, the Broad Institute of MIT and Harvard ... Brazil . Cell, pinpoints ... dogs "escape" the disease,s effects. The Boston Children,s lab ...
(Date:11/10/2015)... 2015  In this report, the biomarkers ... product, type, application, disease indication, and geography. ... are consumables, services, software. The type segments ... efficacy biomarkers, and validation biomarkers. The applications ... development, drug discovery and development, personalized medicine, ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... , ... November 30, 2015 , ... ... globally touring exhibition Jurassic World: The Exhibition, opening in March 2016 at Melbourne ... on a worldwide tour including several North American tour dates. The Exhibition is ...
(Date:11/30/2015)... 2015  HUYA Bioscience International, the leader in accelerating ... innovations, today announced it has signed a Memorandum of ... foster collaboration between KDDF and HUYA with the ultimate ... products for the global market. ... new innovative preclinical and clinical stage compounds. The company ...
(Date:11/30/2015)... Nov. 30, 2015  Northwest Biotherapeutics (NASDAQ: NWBO ... personalized immune therapies for solid tumor cancers, announced today ... independent director, and the Company welcomes Neil Woodford,s ... a recent anonymous internet report on NW Bio.  The ... Linda Powers stated, "We agree with Mr. ...
(Date:11/27/2015)... Kingdom , Nov. 27, 2015 /PRNewswire/--  Mallinckrodt plc ... company, announced today that it has closed the sale ... business to Guerbet (GBT- NYSE Euronext) in a transaction ... encompassed four manufacturing facilities and a total of approximately ... in the St. Louis area. ...
Breaking Biology Technology: