Biology-driven medicine: tissue matters : The Lancet Oncology

Biology-driven medicine: tissue matters : The Lancet Oncology

The Lancet Oncology, Volume 13, Issue 4, Page 319, April 2012

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doi:10.1016/S1470-2045(12)70142-0

 "Deciding who to test, how, and when, will help realise the vast potential of personalised medicine for cancer. However, integration of biology-driven therapy into the clinic is becoming increasingly complex and intratumoral heterogeneity could prove to be the Achilles' heel of targeted therapy in an era in which tissue has become an extremely precious resource that must be used sparingly, pragmatically, and within a multidisciplinary decision-making team."

 The Lancet Oncology

 

"Cancer therapy has been revolutionised by the advent of targeted agents. As a result, patient selection through genetic testing is a rapidly growing industry, but this has posed extra challenges for the patient and oncological team including cost, legal obstacles, test accuracy, and management of tissue. In this context, a recent report in the New England Journal of Medicine suggests intra-tumoral heterogeneity might be an even more complex issue than previously thought. The report showed that up to two-thirds of genetic results in renal-cell carcinoma will vary throughout the tumour specimen when tissue is assessed in a multiregional sequencing analysis. So what are the consequences of this finding for the use of single biopsies to guide treatments in the clinic?............

" Furthermore, according to speakers at the 13th European Congress on Perspectives in Lung Cancer held in Amsterdam, Netherlands, on March 9—10, 2012, the role of the pathologist is paramount in ensuring not only that enough tissue is left after histological diagnosis to do essential tests—such as those to predict benefit from the EGFR inhibitors—but also that testing is not done until the evidence linking the target to the efficacy of the drug, and any potential future treatments, are considered. A multidisciplinary environment is therefore essential to ensure an appropriate discussion of the timing of any pathological testing, and, where possible, to enable tissue to be saved to help guide future decision-making. This point was affirmed in a recent comment in the Journal of Clinical Oncology in which the authors suggested that excluding patients without the proposed target for treatment of breast and gynaecological cancer with PI3K/mTOR inhibitors should not be done until “a stronger predictive relationship emerges”. The comment also acknowledged the challenge of testing for rare mutations. Resistance to therapy can also develop, necessitating further testing to select potential responders to subsequent therapy. Use of blood might help overcome some of the difficulties associated with tissue resources, and several studies have been done using serum samples to define predictors of response to treatment, but these investigations are fraught with difficulties, including linking any serum changes to the tumour itself...........