Translational cancer research 

About: Translational cancer research is an academic journal published by AME Publishing Company. The journal publishes majorly in the area(s): Medicine & Cancer. It has an ISSN identifier of 2218-676X. It is also open access. Over the lifetime, 3096 publications have been published receiving 13590 citations.

DNA double strand break repair via non-homologous end-joining

Abstract: DNA double-stranded breaks (DSB) are among the most dangerous forms of DNA damage. Unrepaired DSBs results in cells undergoing apoptosis or senescence whereas mis-processing of DSBs can lead to genomic instability and carcinogenesis. One important pathway in eukaryotic cells responsible for the repair of DSBs is non-homologous end-joining (NHEJ). In this review we will discuss the interesting new insights into the mechanism of the NHEJ pathway and the proteins which mediate this repair process. Furthermore, the general role of NHEJ in promoting genomic stability will be discussed.

Cancer biomarker discovery and validation

Abstract: With the emergence of genomic profiling technologies and selective molecular targeted therapies, biomarkers play an increasingly important role in the clinical management of cancer patients. Single gene/protein or multi-gene "signature"-based assays have been introduced to measure specific molecular pathway deregulations that guide therapeutic decision-making as predictive biomarkers. Genome-based prognostic biomarkers are also available for several cancer types for potential incorporation into clinical prognostic staging systems or practice guidelines. However, there is still a large gap between initial biomarker discovery studies and their clinical translation due to the challenges in the process of cancer biomarker development. In this review we summarize the steps of biomarker development, highlight key issues in successful validation and implementation, and overview representative examples in the oncology field. We also discuss regulatory issues and future perspectives in the era of big data analysis and precision medicine.

Nanoparticles in radiation therapy: a summary of various approaches to enhance radiosensitization in cancer

Abstract: Acquired radiation resistance is one of the major causes of radio therapy failure and subsequent tumor relapse. Multiple approaches have been utilized to limit the radiation resistance while simultaneously enhancing the efficacy and safety of radiation therapy. The three major approaches for the improvement of radiation therapy have involved (I) ehancing radiosensitization of tumor tissue; (II) rversing of radiation resistance in tumor tissue; and (III) ehancing radioresistance of the healthy tissue. Nanoparticles have played a key role in the enhancement of the radiation therapy by acting both as a therapeutic as well as a carrier for other therapeutics. In this review we summarize the research being carried out using different species of nanoparticles for enhanced radiosensitization in cancer.

DNA damage tolerance: a double-edged sword guarding the genome.

Abstract: Preservation of genome integrity is an essential process for cell homeostasis. During the course of life of a single cell, the genome is constantly damaged by endogenous and exogenous agents. To ensure genome stability, cells use a global signaling network, namely the DNA damage response (DDR) to sense and repair DNA damage. DDR senses different types of DNA damage and coordinates a response that includes activation of transcription, cell cycle control, DNA repair pathways, apoptosis, senescence, and cell death. Despite several repair mechanisms that repair different types of DNA lesions, it is likely that the replication machinery would still encounter lesions that are mis-repaired or not repaired. Replication of damaged genome would result in high frequency of fork collapse and genome instability. In this scenario, the cells employ the DNA damage tolerance (DDT) pathway that recruits a specialized low fidelity translesion synthesis (TLS) polymerase to bypass the lesions for repair at a later time point. Thus, DDT is not a repair pathway per se, but provides a mechanism to tolerate DNA lesions during replication thereby increasing survival and preventing genome instability. Paradoxically, DDT process is also associated with increased mutagenesis, which can in turn drive the cell to cancer development. Thus, DDT process functions as a double-edged sword guarding the genome. In this review, we will discuss the replication stress induced DNA damage-signaling cascade, the stabilization and rescue of stalled replication forks by the DDT pathway and the effect of the DDT pathway on cancer.

Liquid biopsy for cancer screening, patient stratification and monitoring

Abstract: Molecular characterization of a patient’s tumor to guide treatment decisions is increasingly being applied in clinical care and can have a significant impact on disease outcome. These molecular analyses, including mutation characterization, are typically performed on tissue acquired through a biopsy at diagnosis. However, tumors are highly heterogeneous and sampling in its entirety is challenging. Furthermore, tumors evolve over time and can alter their molecular genotype, making clinical decisions based on historical biopsy data suboptimal. Personalized medicine for cancer patients aims to tailor the best treatment options for the individual at diagnosis and during treatment. To fully enable personalized medicine it is desirable to have an easily accessible, minimally invasive way to determine and follow the molecular makeup of a patient’s tumor longitudinally. One such approach is through a liquid biopsy, where the genetic makeup of the tumor can be assessed through a biofluid sample. Liquid biopsies have the potential to help clinicians screen for disease, stratify patients to the best treatment and monitor treatment response and resistance mechanisms in the tumor. A liquid biopsy can be used for molecular characterization of the tumor and its non-invasive nature allows repeat sampling to monitor genetic changes over time without the need for a tissue biopsy. This review will summarize three approaches in the liquid biopsy field: circulating tumor cells (CTCs), cell free DNA (cfDNA) and exosomes. We also outline some of the analytical challenges encountered using liquid biopsy techniques to detect rare mutations in a background of wild-type sequences.