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This Perspective highlights the sources and functions as well as the evaluation of biomarkers that are useful in cancer, with a focus on those biomarkers that are most relevant for identifying patients who are likely to respond to a given therapy, and those biomarkers that are most effective for measuring patient response to therapy. This Perspective highlights biomarkers that are expressed as a consequence of cancer development and progression. We focus on those biomarkers that are most relevant for identifying patients who are likely to respond to a given therapy, as well as those biomarkers that are most effective for measuring patient response to therapy. These two measures are necessary for selecting the right drug for the right patient, regardless of whether the setting is in drug development or in the post-approval use of the drug for patients with cancer. We also discuss the innovative designs of clinical trials and methodologies that are used to validate and qualify biomarkers for use in specific contexts. Furthermore, we look ahead to the promises and challenges in the field of cancer biomarkers.

This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).

Human colon cancer develops in a stepwise fashion from normal mucosa to adenomatous polyps to carcinoma. Mutation in the adenomatous polyposis coli ( APC ) gene commonly occurs early in the development of sporadic adenomas. 1 Patients with familial adenomatous polyposis have an inherited germ-line APC mutation 2 that results in hundreds of adenomatous polyps and a nearly 100 percent risk of colon cancer. Management includes prophylactic proctocolectomy, or colectomy followed by sigmoidoscopic surveillance and rectal polypectomy. Because the adenoma-to-carcinoma sequence in familial adenomatous polyposis resembles sporadic colon carcinogenesis, 1 studies of familial adenomatous polyposis may contribute to the prevention of sporadic adenomas . . .

Background Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG‐PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5‐point scale (5‐PS). Methods In CALGB 50303, patients with DLBCL received frontline R‐CHOP or DA‐EPOCH‐R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5‐PS with progression‐free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. Results Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. Conclusions These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials. In this retrospective analysis of CALGB 50303 study, Torka et al. found that associations with PFS and OS when applying local review versus central review of interim PET (iPET) were comparable? SUV = 66% at iPET was associated with PFS and OS, but visual scoring systems (VSS) were not, highlighting the limitations of VSS.

The high‐content interrogation of single cells with platforms optimized for the multiparameter characterization of cells in liquid and solid biopsy samples can enable characterization of heterogeneous populations of cells ex vivo. Doing so will advance the diagnosis, prognosis, and treatment of cancer and other diseases. However, it is important to understand the unique issues in resolving heterogeneity and variability at the single cell level before navigating the validation and regulatory requirements in order for these technologies to impact patient care. Since 2013, leading experts representing industry, academia, and government have been brought together as part of the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium to foster the potential of high‐content data integration for clinical translation.

Key Points Focusing development efforts for cancer-preventive drugs on precancerous lesions (that is,intraepithelial neoplasia (IEN)) can reduce costs and accelerate the emergence of new cancer-preventive drugs. IEN addresses both risk and clinical endpoints, as it is part of the process of neoplastic progression and not just a biomarker of it. Examples of IEN conferring high risk for progression are colorectal adenomas, breast ductal carcinoma in situ (DCIS), oral dysplasia, high-grade prostatic intraepithelial neoplasia (PIN), Barrett oesophagus and dysplastic nevi. Risk of progression is best estimated by combining IEN with other risk markers/factors. Examples of cancer-prevention clinical endpoints that involve IEN include treatment and prevention of colorectal adenomas, treatment of oral dysplasia, prevention of DCIS and treatment of Barrett oesophagus. In addition to cancer prevention, clinical benefits include reduced morbidity, reduced cost and increased availability of treatment. Several drugs have shown promising efficacy in preventing cancers and in preventing and treating IEN (for example,tamoxifen, raloxifene, celecoxib, finasteride, toremifene, tea polyphenols and statins), but some have also encountered problems that provide lessons that can be applied in future strategies to bring cancer-preventive drugs to market. Demonstrating long-term drug safety is the toughest challenge. Because target populations for cancer-prevention drugs are asymptomatic, and might take the drugs for many years, little toxicity can be tolerated. Methods must be developed to detect and evaluate significant toxicities that occur rarely, and any toxicity that occurs across multiple trials. This might be improved by rigorous post-marketing surveillance. Can the process of new cancer-preventive drug development be improved by focusing on precancer (intraepithelial neoplasia) to better identify subjects at risk and prove efficacy in shorter, smaller trials? Despite significant interest from the research community and the population in general, drug approvals for cancer prevention and/or cancer risk reduction are few. This is due, in part, to the requirement that new cancer-preventive drugs must first be shown to be efficacious in reducing cancer incidence or mortality. Moreover, such drugs need to have proven safety for long-term administration. This process can be improved by focusing on precancer (intraepithelial neoplasia) to identify subjects at risk and prove efficacy in shorter, smaller trials as well as on detecting early markers of potential toxicities of chronic exposure to cancer-preventive drug regimens.

Cancer chemoprevention can be defined as prevention of cancer by the administration of one or more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. Based largely on the time period that chemopreventive agents exhibit activity in animal models of carcinogenesis, they can be classified as inhibitors of carcinogen formation, blocking agents, and suppressing agents. The majority of compounds that inhibit the formation of carcinogens prevent the formation of nitrosamines from secondary amines and nitrite in an acidic environment. Blocking agents are inhibitors of tumor initiation, while suppressing agents are inhibitors of tumor promotion/progression. Many well-characterized chemopreventive agents act at one or more steps in both tumor initiation and promotion/progression. The objective of this paper is to provide a general discussion of the mechanisms through which chemopreventive agents inhibit carcinogenesis. Examples of agents that act through these mechanisms are given; however, a complete listing of effective chemopreventive agents is not possible within the context of this paper. At the conclusion is a brief discussion of future prospects in cancer chemoprevention and obstacles to overcome.

The promise of in vivo molecular imaging in oncology.