Biology-driven medicine: tissue matters : The Lancet Oncology
The Lancet Oncology, Volume 13, Issue 4, Page 319, April 2012
"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."
"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...........
