Profiling genetic alterations in cancer with drug sensitivity is a way to develop a tailored approach to treating patients with cancer, researchers from Europe and the USA reported in the journal Nature. In what they describe as the “largest study of its kind”, hundreds of associations between cancer gene mutations and anticancer medication sensitivity or resistance have been uncovered.

The team found that, for example, a medication currently used for ovarian and breast cancer was effective in treating Ewing’s sarcoma, a childhood bone cancer. As the drug has relatively low toxicity, it might be considered as a safer option for kids and young adults with Ewing’s sarcoma; an aggressive cancer.

The authors explain that genetic changes that occur in cancers are intimately related to how a drug works. Anti-cancer drug sensitivity is influenced by mutations that occur in the cancer genes. Large-scale studies that examine this relationship should produce several effective cancer treatments which are tailored to the specific features of a patient’s disease.

First author, Dr Mathew Garnett, from the Wellcome Trust Sanger Institute, said:

“Our key focus is to find how to use cancer therapeutics in the most effective way by correctly targeting patients that are most likely to respond to a specific therapy. We studied how genetic changes in a panel of more than 600 cancer cell lines effects responses to 130 anti-cancer drugs, making it the largest study of this type to date.”

Biological markers of drug sensitivity were identified and linked to a wide range of oncology medications. Most of the genes they analyzed were closely linked to either resistance or sensitivity to at least one of the medications they were testing and analyzing.

Senior author, Dr Cyril Benes, from Massachusetts General Hospital Cancer Centre, explained:

“Our research has taken us down unknown paths to find associations that are completely novel. We have identified hundreds of associations, many of which we still don’t fully understand. We identified a novel indication for the use of PARP inhibitors, anti-cancer drugs currently used to treat breast and ovarian cancers, for the treatment of Ewing’s sarcoma.”

Patients with Ewing’s sarcoma who have relapsed after chemotherapy, or whose cancer has spread, have a 15% chance of surviving beyond five years. PARP inhibitors are to be tested in clinical trials, and it is expected they will improve Ewing’s sarcoma patients’ outcomes.

Senior author, Dr Ultan McDermott, from the Wellcome Trust Sanger Institute, said:

“Advances in next-generation sequencing technologies are already being translated into the large-scale detection of cancer gene mutations in the clinic. There is a compelling need to identify, in a systematic fashion, whether observed mutations affect the likelihood of a patient’s response to a given drug treatment.

We have therefore developed a unique online open-access resource for the research and medical community that can be used to optimise the clinical application of cancer drugs as well as the design of clinical trials of investigational compounds being developed as treatments.”

The team’s database, an open-access one, is expected to become a major resource for cancer research scientists, resulting in better therapy for patients with cancer.

This is a 5-year collaboration between The Wellcome Trust Sanger Institute, the Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, and The Cancer Genome Project.

Senior author, Professor Daniel Haber, from Massachusetts General Hospital Cancer Centre, said:

“Our work is helping to move cancer therapeutics away from the conventional tissue-based treatment to a more molecular-based treatment. The next steps for this collaborative project are to evaluate some of the key findings using tumour samples and test new candidate therapeutic strategies in clinical trials so we can hopefully improve the way we treat cancer patients. We are continuing our screening effort, in particular using drug combinations to discover innovative and better therapeutic options.”

Christian Nordqvist