Molecular profiling and targeted treatments in cancer: translating subtypes into clinical practice

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Last year, it was revealed that breast cancer can be split into 10 different diseases in a landmark study that could revolutionize how it is treated. In a video Q&A published in BMC Medicine, we talk to study lead Carlos Caldas from Cancer Research UK Cambridge Institute about their findings. Caldas discusses the difficulties associated with current tumor stratification based on HER2 and estrogen receptor (ER) expression, emphasizing that genetic subtyping will permit more precise risk profiling in the future, along with the development of novel therapies. Caldas describes how toxic treatments could be withheld from women in groups with excellent survival rates, whereas those with poor prognosis could be prioritized for trials of new therapies.

In a minireview article, Richard Baird and Carlos Caldas further explore the potential of molecular profiling and discuss how genomic studies can be applied in a more individualized approach to breast cancer treatment. The authors describe the need for repeat tumor biopsies in order to monitor genetic variation over time, and emphasize that genetic diversity must be considered in clinical trials for new therapies.

While the results of molecular profiling studies should have an enormous impact on breast cancer treatment, they must now be validated further before they can be used routinely in the clinic. Many current trials for breast cancer aim to establish the best treatment regimen based on HER2 and ER-targeted treatments. The results of such trials were presented at the recent annual meeting of the American Society of Clinical Oncology (ASCO 2013), where the speakers discussed different strategies to overcome resistance to HER2-targeted treatment. Lisa Carey and David Ollila from UNC-Chapel Hill described the results of the CALGB40601 trial, where dual HER2 targeting with trastuzumab plus lapatinib improved outcome for HER2 positive breast cancer patients. Ruth O’Regan from Emory University explained how inhibiting MTOR proteins can help overcome resistance to trastuzumab, and showed that everolimus, an MTOR inhibitor, improves progression-free survival when added to trastuzumab treatment in the BOLERO-3 trial.

The theme of targeted therapy continued throughout the meeting, with interesting presentations on clinical trials for lung cancer. David Planchard from the Gustarve Roussy Institute presented new phase II results showing that dabrafenib is a promising therapeutic option for non-small cell lung cancer (NSCLC) patients with BRAF mutations. Alice Shaw from Massachusetts General Hospital described recent progress in treating another subtype of lung cancer defined by ALK gene rearrangements (Alk+), showing that LDK378, a new agent developed from crizotinib, causes tumor shrinkage in Alk+ NSCLC patients.

As highlighted by data presented at ASCO 2013, there are now multiple molecular markers defining smaller disease groups across many types of cancer, and it is important that these results are translated effectively into clinical practice. Lisa McShane from the National Cancer Institute outlined the challenges associated with carrying out clinical trials in the era of molecular profiling, and described the different trial designs that can be used. McShane emphasized that scientists and clinicians should be prepared to deal with ever-moving targets as more biomarkers are discovered, and explained how we expect to see bigger treatment effects when targeted therapies are given.

We look forward to seeing how current molecular profiling studies impact cancer treatment in the future. Although many challenges still remain, as reviewed by Wei Xu and colleagues in BMC Medicine, further development of genomic biomarkers should lead to improved patient stratification and a more personalized approach to cancer treatment.