Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
My Interpretation of The Abstract
Brain metastases are often associated with depression. Whether brain metastases have certain genetic alterations other than those observed in primary tumors not known. Gene sequencing techniques were performed and there were 86 different samples brain metastases, primary tumors and normal tissue found. In all identically related cancer samples, all metastatic and primary sites shared a common origination yet continued to evolve independently. In 53% of cases, it was found that possible alterations in the brain metastases were not detected in the matched primary-tumor sample. However, shape wise and time wise, the separated brain metastasis sites were genetically the same. Detached/separated extracranial and regional lymph node metastases were developing in all different directions in relation to the brain metastases. Alterations associated with sensitivity to PI3K/AKT/ mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases were detected. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases.
Precision Medicine
Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.
PI3K inhibitors
A phosphoinositide 3-kinase inhibitor (PI3K inhibitor) is a class of medical drug that functions by inhibiting one or more of the phosphoinositide 3-kinaseenzymes, which are part of the PI3K/AKT/mTOR pathway, an important signaling pathway for many cellular functions such as growth control, metabolism and translation initiation.
CDK inhibitors
​Progression of the cell cycle driven by CDKs. Mitogenic signals stimulate cyclin-dependent kinase 4 (CDK4) and CDK6 and promote entry into the cell cycle, whereas antiproliferative checkpoints inhibit CDK4 and CDK6 activity or induce the expression of the CDK4 and CDK6 inhibitor p16INK4A
Genomics
Genomics refers to the study of the genome in contrast to genetics, which refers to the study of genes and their roles in inheritance. Genomics can be considered a discipline in genetics. It applies recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes (the complete set of DNA within a single cell of an organism).
Brain Metastases
A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body. As primary cancer treatments such as surgery, radiation therapy and chemotherapy have become more effective in the past few decades, people with cancer are living longer after initial treatment than ever before. However, brain metastases still occur in many patients months or even years after their original cancer treatment. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.
Evolutionary Patterns
​Evolution over time can follow several different patterns. Factors such as environment and predation pressures can have different effects on the ways in which species exposed to them evolve. shows the three main types of evolution: divergent, convergent, and parallel evolution