Molecular imaging and targeted therapies

Abstract

Targeted therapeutic and imaging agents are becoming more prevalent, and are used to treat increasingly smaller segments of the patient population. This has lead to dramatic increases in the costs for clinical trials. Biomarkers have great potential to reduce the numbers of patients needed to test novel targeted agents by predicting or identifying non-response early-on and thus enriching the clinical trial population with patients more likely to respond. Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers can be used to predict response to specific therapies, predict response regardless of therapy, or to monitor response once a therapy has begun. In terms of drug development, predictive biomarkers have the greatest impact, as they can be used as inclusion criteria for patient segmentation. Prognostic markers are used routinely in clinical practice but do not provide direction for the use of targeted therapies. Imaging biomarkers have distinct advantages over those that require a biopsy sample in that they are “non-invasive” and can be monitored longitudinally at multiple time points in the same patient. This review will examine the role of functional and molecular imaging in predicting response to specific therapies; will explore the advantages and disadvantages of targeting intracellular or extracellular markers; and will discuss the attributes of useful targets and methods for target identification and validation.

Synthetic lethal screening reveals FGFR as one of the combinatorial targets to overcome resistance to Met-targeted therapy

“…Although the relationship between Met and other RTKs in the survival of Met drug resistant cancer cells remains uncertain, it has been shown that Met inhibitor-driven resistance could be rescued by inactivation of fibroblast growth factor receptor (FGFR) by small molecules 29,30 . Recently, many approaches have focused on discovering biomarkers for patient selection and exploring novel combination therapies 31 . To systematically identify targets whose inhibition would increase the response of cancer cells to Met inhibitors, we performed medium-throughput siRNA library synthetic lethal screening targeting genes associated with systems biology-derived EGFR and Met signaling pathways 32 .…”

A Catalyzing Phantom for Reproducible Dynamic Conversion of Hyperpolarized [1-13C]-Pyruvate

“…Imaging measurements are particularly attractive because they can provide researchers and clinicians with non-invasive, serial views of heterogeneous tumor tissue in toto, in stark comparison to the limited number of samples that are practically available through traditional biopsy [1]. In order for imaging biomarkers to provide additional information that positively affects clinical decisions, they must be robust, reproducible, and reflective of relatively specific tissue characteristics.…”

A sucrose-derived scaffold for multimerization of bioactive peptides

“…1–4 One strategy for development of such reagents involves attaching imaging agents to molecular scaffolds that bear multiple copies of ligands to receptors present on the surface of cancer cells. 5–11 Such multivalent constructs could display enhanced affinity and selectivity for cancer cells based on cooperative binding.…”