How Imaging Biomarkers Can Inform Clinical Trials and Clinical Practice in the Era of Targeted Cancer Therapy.

Individualized therapy for patients with cancer, often termed personalized or precision medicine, has become an increasingly important topicwith the recognition that tumors once classified solely by their tissue of origin consist of multiple genetically distinct subgroups. This ability to categorize tumors into small subgroups defined by molecular makeup can have an important impact on treatment approach because some tumors are driven by a molecular abnormality that can be targeted by specific drugs. Targeted therapies are available for tumors that express theestrogen receptor (ER) (tamoxifen, letrozole), HER2 (trastuzumab, pertuzumab), EGFR (gefitinib), the BCR-ABL fusion protein kinase (imatinib), the BRAF V600E protein kinase (vemurafenib),PD-1 ligands (pembrolizumab),andVEGF (bevacizumab), to name a few. However,questionsremainforhowbesttousethese therapies. How can patients most likely to benefit from targeted therapy be easily and reliably identified? How should responsebemeasured (especially becausemany targetedtherapiesarecytostatic)?Historically,thesequestions have been addressed by assaying tissue or serum biomarkers. However, molecular imaging offers several advantages as a cancer biomarker and is complementary to tissue sampling. Because imaging is noninvasive andnondestructive, it is capableof serialmeasurements of the same tissue over time, and it can be used to interrogate lesions that aredifficult or impossible to safelybiopsy. Imaging can also capture heterogeneity within individual lesions and across all lesions in a patient. In addition, imaging can reflect the local in vivomicroenvironment of the tumor in an unperturbed state aswell as in response to therapy, and in ways not adequately represented by in vitro assays.