Detecting Tumor Metastases

Abstract

Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process.

Theranostic Tripartite Cancer Terminator Virus for Cancer Therapy and Imaging

“…When combining these engineered viruses with additional therapeutic agents (including radiation, chemotherapy, immunotherapy, and gene therapy), in specific instances enhanced clinical endpoints have been achieved, but even these combinations have not proven universally effective, particularly in the context of patients with metastases [ 68 , 71 ]. A further limitation of the current therapies for cancer metastases, which is the primary cause of morbidity (estimated to be 90%) in patients with solid cancers, is the inability to accurately locate metastatic tumor cell populations and to appropriately deliver therapeutic payloads in tumor cells or the tumor microenvironment [ 2 , 3 , 4 ].…”

“…To achieve this objective, we relied on the minimal PEG -3 promoter [ 62 , 63 ], which is regulated by AP1 and PEA3 transcription factors, and expresses selectively in both cancerous murine and human cells, with minimal expression in normal cells [ 44 , 63 , 64 , 65 ]. Additionally, we have shown that the minimal PEG -3 promoter, an essential part of the CTV , can also be used to image metastatic cancer cells (including prostate, breast, and melanoma) non-invasively (using luciferase or thymidine kinase reporter genes) in pre-clinical animal models [ 1 , 2 , 3 ]. Based on these considerations, we initially attempted to generate a tripartite adenovirus in which both the viral Ad.5 E1A gene-regulating replication and the imaging luciferase gene were regulated independently by two copies of the minimal PEG -Prom, and also containing mda-7/IL-24 transcriptionally regulated by the cytomegalovirus ( CMV ) promoter.…”

“…Noninvasive imaging for cancer diagnosis, as a means of guiding therapy, is critical for improving clinical outcomes in patients with diverse localized and distant (metastatic) tumors [ 1 , 2 , 3 ]. Although there have been significant refinements in imaging approaches and therapies for cancers, detection and therapy for metastasis remain imprecise with limited effectiveness, [ 4 ].…”

Carotenoids in Cancer Metastasis—Status Quo and Outlook

“…The metastatic processes’ mechanisms are complicated and involve multiple signaling molecules and pathways [ 1 ]. As one of the hallmarks of cancer [ 2 , 3 ], metastasis is often the cause of treatment failure [ 1 ]. In addition, patients receiving chemotherapy often acquire drug resistance, which eventually leads to cancer recurrence and metastasis [ 4 ].…”

“…Although the prevention or early diagnosis of cancer certainly improves clinical outcomes [ 5 ], cancer is diagnosed frequently in advanced stages associated with metastasis [ 6 ]. Thus, the early detection of metastatic cancer and appropriate therapeutic interventions are key considerations in managing advanced cancer patients [ 3 ]. The main obstacle of current treatment modalities is the heterogeneity of metastasis associated with the difference of metastatic tumors from the primary tumor, as well as additional alterations at both the genetic and epigenetic levels.…”