In spite of several novel treatments becoming available in recent years, most cancers remain incurable. A fraction of cells survive the treatment (as minimal residual disease) and eventually lead to relapse. The central problem is that many treatments either themselves exploit and/or induce DNA damage, or they are combined with agents (such as melphalan) which induce DNA damage. Such treatments, although they kill cancer cells, also increase genomic instability in remaining cancer cells and normal cells. Since genomic instability serves as a tool for acquisition of genomic and functional changes required for disease progression, it is necessary that we elucidate mechanisms underlying genomic instability to delineate pathogenesis, overcome drug resistance, and develop therapeutics which would target and not assist genomic evolution.
The ability to constantly evolve not only enables the cancer cell to acquire new characteristics aiding the development and progression of disease, but also presents a great challenge for cancer treatment and diagnosis. Moreover, changes acquired as a consequence of genomic instability may predict patient outcomes. Genomic instability can be a consequence of a number of factors which can be extrinsic, such as exposure to harmful agents in food and environment, or intrinsic, such as food metabolites and/or aberrations in pathway/s involved in genome maintenance. The mechanisms underlying genomic instability and their activation during carcinogenesis are not fully understood, and identification of these mechanisms (both extrinsic and intrinsic) could help in the development of novel strategies for cancer prevention and treatment.
Recently, whole exome and whole genome sequencing have been leveraged to define specific mutational signatures and types of clonal evolution which can give insight into mechanisms and processes underlying genomic instability in cancer. Similarly, the application of these powerful approaches on single cells has further revolutionized the field of genomics and cancer research. Although some of these tools have led to the identification of novel targets, it still remains to be seen: 1) If mutational signatures can accurately predict corresponding activity; 2) Does a specific signature and its mediator remain the same in a normal vs. cancer environment; 3) How reproducible are these signatures or the areas of genome they affect; 4) How do newer techniques/tools compare to other platforms, for example RNASeq vs. microarray?; 5) How accurate is the application of these techniques on a single cell? Similarly, the role of inflammation and the tumor microenvironment has also emerged as being of great significance in translational cancer research.
This Research Topic invites Review and Original Research papers describing recent findings in the fields of genomics and genomic evolution, inflammation, and/or the tumor microenvironment, investigating the following:
-Validation and translational relevance of mutational signatures, clonal dynamics and other information derived from whole exome, genome and RNA sequencing.
-Comparisons between newer sequencing technologies and older methods.
- Molecular mechanisms and consequences of genomic instability and inflammation in cancer. Manuscripts may provide novel information in these fields separately or link them together.
- Validation of new prognostic tools and novel therapeutic strategies targeting genomic instability, telomere maintenance, and inflammation.
- Identification of new potential carcinogens and new ideas to reduce exposure and/or prevent new genomic changes resulting in the development or progression of cancer.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
In spite of several novel treatments becoming available in recent years, most cancers remain incurable. A fraction of cells survive the treatment (as minimal residual disease) and eventually lead to relapse. The central problem is that many treatments either themselves exploit and/or induce DNA damage, or they are combined with agents (such as melphalan) which induce DNA damage. Such treatments, although they kill cancer cells, also increase genomic instability in remaining cancer cells and normal cells. Since genomic instability serves as a tool for acquisition of genomic and functional changes required for disease progression, it is necessary that we elucidate mechanisms underlying genomic instability to delineate pathogenesis, overcome drug resistance, and develop therapeutics which would target and not assist genomic evolution.
The ability to constantly evolve not only enables the cancer cell to acquire new characteristics aiding the development and progression of disease, but also presents a great challenge for cancer treatment and diagnosis. Moreover, changes acquired as a consequence of genomic instability may predict patient outcomes. Genomic instability can be a consequence of a number of factors which can be extrinsic, such as exposure to harmful agents in food and environment, or intrinsic, such as food metabolites and/or aberrations in pathway/s involved in genome maintenance. The mechanisms underlying genomic instability and their activation during carcinogenesis are not fully understood, and identification of these mechanisms (both extrinsic and intrinsic) could help in the development of novel strategies for cancer prevention and treatment.
Recently, whole exome and whole genome sequencing have been leveraged to define specific mutational signatures and types of clonal evolution which can give insight into mechanisms and processes underlying genomic instability in cancer. Similarly, the application of these powerful approaches on single cells has further revolutionized the field of genomics and cancer research. Although some of these tools have led to the identification of novel targets, it still remains to be seen: 1) If mutational signatures can accurately predict corresponding activity; 2) Does a specific signature and its mediator remain the same in a normal vs. cancer environment; 3) How reproducible are these signatures or the areas of genome they affect; 4) How do newer techniques/tools compare to other platforms, for example RNASeq vs. microarray?; 5) How accurate is the application of these techniques on a single cell? Similarly, the role of inflammation and the tumor microenvironment has also emerged as being of great significance in translational cancer research.
This Research Topic invites Review and Original Research papers describing recent findings in the fields of genomics and genomic evolution, inflammation, and/or the tumor microenvironment, investigating the following:
-Validation and translational relevance of mutational signatures, clonal dynamics and other information derived from whole exome, genome and RNA sequencing.
-Comparisons between newer sequencing technologies and older methods.
- Molecular mechanisms and consequences of genomic instability and inflammation in cancer. Manuscripts may provide novel information in these fields separately or link them together.
- Validation of new prognostic tools and novel therapeutic strategies targeting genomic instability, telomere maintenance, and inflammation.
- Identification of new potential carcinogens and new ideas to reduce exposure and/or prevent new genomic changes resulting in the development or progression of cancer.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
