The genetic mechanisms underlying cancer have been the focus of research by scientists and medical professionals worldwide. The human genome has undergone random insertions of small DNA fragments known as “jumping genes” during the history of evolution. Transposable elements, another name for these specific DNA pieces, have been linked to the development and spread of cancer. Recent discoveries reported in the online edition of Nature Genetics by researchers from Washington University reveal that transposable elements found in various cancer types could be harnessed to direct groundbreaking immunotherapies toward tumors that typically exhibit resistance to immune-based treatments.
What are Jumping Genes?
Jumping genes, scientifically known as transposable elements or transposons, are unique stretches of DNA that have the ability to move within the genome. Unlike typical genes that remain stationary, jumping genes have the capability to relocate themselves to different positions on the DNA strand. This movement can impact the regulation of nearby genes, leading to significant changes in cellular functions.
Unveiling the Link to Cancer
Scientists have discovered a clear link between jumping genes and a variety of disorders, including cancer, throughout the years. By interfering with the normal operation of genes essential to cell growth control and DNA repair, the study claims that these mobile genetic components can aid in creating and spreading tumors.
A range of malignancies, notably skin and lung cancers, which have a high prevalence of mutation, have shown positive results when treated with immunotherapy. These mutations give rise to unusual proteins, ‘tumor antigens’ that can distinguish tumor cells from normal cells and are good immunotherapy targets. Immunotherapeutic approaches like antibodies, vaccines, and genetically modified CAR-T cell treatments target these tumor antigens. However, certain tumor types have a low mutation burden, posing a challenge for the immune system to identify them as malignant.
The Role of Jumping Genes in Immunotherapies
Immunotherapy has emerged as a highly promising strategy in cancer treatment. However, numerous types of tumors that exhibit low mutation rates have shown resistance to currently available medications. This groundbreaking research sets the stage for identifying tumor antigens in previously immune therapy-resistant cancer types, unveiling new possibilities in the field of cancer immunotherapy.
Jumping genes are usually found in inactive parts of the genome that exist in mature tissues and are believed to have likely come from viruses. However, earlier studies conducted by the research team have shown that these mobile genetic elements can sometimes act as hidden switches, causing a gene to remain turned on continuously, even when it shouldn’t. These sneaky switches can generate abnormal protein fragments that are specific to the tumor and not present in normal cells, thus contributing to the advancement of cancer.
In a groundbreaking study, researchers looked at 33 distinct varieties of cancer from the National Cancer Institute’s The Cancer Genome Atlas Program. The analysis led to the discovery of a remarkable 1,068 transposable element-derived transcripts, which are RNA segments created by cancer cells. These transcripts possess the extraordinary capability to generate tumor antigens, thus presenting themselves as potential targets for the development of innovative immunotherapies.
According to the research team, these prospective tumor antigens are present on the exteriors of cancerous cells, rendering them highly suitable targets for immunotherapy. A noteworthy discovery reveals that nearly 98% of the 10,000+ scrutinized cancer cases encompassed a minimum of one potential antigen target originating from a transposable element. The majority of cancers have the capacity to generate anywhere from two to 75 antigens.
In a noteworthy discovery, it was observed that a large portion of potential proteins with antigenic properties was identified across diverse cancer types and, in certain instances, across multiple tumor categories as well. The research team speculated about the possibility of a universal antigen-based therapy that could effectively treat various malignancies using a single concoction that targets numerous prevalent tumor antigens generated by jumping genes. Notably, the findings suggest that a vaccination comprising 20 highly prevalent protein targets could potentially provide protection to approximately 75% of patients afflicted with 27 distinct types of cancer.
The authors expressed the potential of their analysis, stating that it could lead to the development of a cancer vaccine. The vaccine would specifically target the most common tumor proteins resulting from the top five or ten transposable elements. While this concept of vaccination is currently theoretical, there is an optimistic outlook regarding its effectiveness, as these shared targets have the potential to address a significant portion of malignancies. This study holds promise as a catalyst for the creation of effective immunotherapies across various types of cancer, but further extensive research is necessary to progress in this direction.
The association of jumping genes within cancer cells has opened up a new frontier in cancer immunotherapy. Researchers want to create tailored vaccinations that can strengthen the body’s immune system by harnessing the potential of mobile transposable elements.
Dr. Tamanna Anwar is a Scientist and Co-founder of the Centre of Bioinformatics Research and Technology (CBIRT). She is a passionate bioinformatics scientist and a visionary entrepreneur. Dr. Tamanna has worked as a Young Scientist at Jawaharlal Nehru University, New Delhi. She has also worked as a Postdoctoral Fellow at the University of Saskatchewan, Canada. She has several scientific research publications in high-impact research journals. Her latest endeavor is the development of a platform that acts as a one-stop solution for all bioinformatics related information as well as developing a bioinformatics news portal to report cutting-edge bioinformatics breakthroughs.