‘Liquid-Tumor Biopsies' and the Future of Solid Tumor Oncology

no) additional tissue present for laboratory-based investigation. As a result, there has been considerable and increasing effort by academic and commercial groups to develop a reliable and clinically useful ‘liquid tumor’ biopsy strategy in a number of clinical settings. Such approaches have included both the examination of single cells (‘circulating tumor cells’) as well as free DNA in the blood that is suggested to originate from cancer present within the body. The goals of these efforts are severalfold. First, simply the presence or a calculated number of ‘circulating’ cells might provide prognostic data regarding the individual cancer. Further, with evidence of progression, an alternative therapeutic strategy may be considered even before there is ‘clinical evidence’ (e.g., new or worsening symptoms, changes in imaging studies or blood-based biomarkers) of the ineffectiveness of the current management. Second, and ultimately a far more relevant aim, it has been hoped that the particular molecular findings discovered within the blood from the circulating cells or DNA may permit a ‘window’ into unique molecular changes present within the individual patient’s cancer that will allow for the selection of specific ‘targeted therapeutics’ designed to favorably impact those abnormalities. A strong argument can be advanced that one of the critical distinguishing features associated with advances in the management of hematologic malignancies, in contrast to solid tumors, has been the ease of availability of ‘tissue’ during the natural history of the illness in the former to both study the biology of the malignancy and increasingly carefully monitor changes during the course of the cancer at the molecular level in individual patients. It is currently ‘standard-of-care’, for example, to examine the blood or bone marrow to document the depth of a molecularly defined ‘complete response’ in patients with chronic myelocytic leukemia to both determine the extent of response and to document the presence of resistance to the current therapy long before there is any other evidence this event has occurred. Such early warning may permit critically relevant modifications in therapy that will favorably impact patient outcomes. Further, in the not-so-distant past, there was almost always a substantial amount of cancer available from solid tumors to at least examine for the presence of unique genomic profiles at diagnosis. However, with the increasing use of minimally invasive procedures to confirm the presence of cancer and the subsequent relatively early delivery of systemic antineoplastic drug therapy in the natural history of a given malignancy, there may be limited (or Published online: May 26, 2016