Cancer is caused by changes in DNA – the genetic material that controls cell function. In most cases, cancer is the result of uncontrolled cell division due to abnormalities in the DNA. Some of these changes may be inherited, but some may be sporadic.
Each type of cancer may have a unique set of genetic mutations. Specific changes in DNA can serve as targets of therapy for each individual. Tumor DNA testing or genetic profiling of cancer is always necessary to determine the unique changes in DNA that have led to carcinogenesis.
DNA sequencing and analysis of a sample from a patient’s tumor determines the arrangement of the four bases—A, T, G, and C. Human cells contain about 6 billion bases, which is about 6 gigabytes of data. Sequence errors in cancer can include mutations, translocations and copy number alterations.
DNA sequencing for cancer treatment
1. Determining the Presence of Specific Known Mutations in Samples for Individualized Cancer Treatment
Not every genetic abnormality results in cancer. However, particular mutations may be a hallmark of specific types of cancer. For example, mutations in the EGFR gene are present in many non-small cell lung cancers (NSCLCs). Today, a group of drugs are available that selectively counteract the effects of the EGFR gene mutation. Therefore, anyone diagnosed with NSCLC can have their tumor DNA sequenced to check whether they have an EGFR mutation so that they can benefit from specialized treatment.
At elite cancer research and treatment centers such as Dana Farber, genetic profiling is a part of the profile program. Under this screening process, the patient’s DNA sample is scanned for thousands of known mutations and abnormalities commonly associated with particular types of cancer.
The results of tumor DNA sequencing and analysis often reveal which patients are ideal for receiving targeted treatment or personalized medicine or new treatments as part of clinical trials. For example, as part of new research at Memorial Sloan Kettering Cancer Center (MSKCC), scientists found that 37% of more than 10,000 tumor biopsies samples had one or more mutations that could be addressed with existing treatments and drugs. could have been done.
2. Revealing the evolution of treatment/drug resistance in post-treatment cancer cells
At the same time, large-scale sequencing projects such as The Cancer Genome Atlas (TCGA) contain data from thousands of whole-exome sequencing (WES) responses. Comparative studies involving data from TCGA can be used to explore how cancers gradually change their genetic stripes.
Additionally, sequence comparison data from tumors before and after treatment can provide healthcare professionals and researchers with an understanding of the mechanism by which some types of cancer become resistant to treatment. Elucidating the mechanisms of resistance to therapy in specific cancers may help researchers determine alternative and more effective courses of treatment.
For example, researchers at the Center for the Prevention of Progression of Blood Cancer at Dana Farber collect tissue samples from individuals with preexisting conditions that potentially develop into multiple myeloma and other hematological cancers. Genetic sequencing of these samples could help researchers understand the development of these diseases and develop drugs that can stop disease progression at the earliest possible stages.
Plus, read about what blood cancer is, symptoms, causes, types, and treatment.
3. Identifying Genomic Biomarkers and Predicting the Efficiency of Immunotherapy for Specific Cancer Types
Several studies have shown the potential for treating several types of cancer using checkpoint inhibitors in the human immune system. Immunotherapy is particularly useful in the treatment of pre-treatment and recurrent cancer forms. These studies identify genomic biomarkers and their types in healthy versus cancer cells.
For example, over-activation of the anti-PD-1/PF-1 gene is found in specific types of cancer such as lymphoma. On the other hand, lung cancer, melanoma and MSI-positive colorectal cancer exhibit a high mutation load throughout the genome. Treatment of different types of cancer using immunotherapy shows different levels of efficacy.
HLA presentations and mutations of the INF-gamma pathway are often related to resistance to immunotherapy. WES and whole genome sequencing (WGS) elucidate DNA sequences within cancer cells that are vulnerable to immunotherapy. New-age DNA sequencing and analysis techniques elucidate the neoantigen signature and the quality and quantity of immune cells from tumor samples (pre-treatment and post-treatment) as well as from immune cells used in immunotherapy.
Check out our list of the best cancer hospitals in India.
Why is the impact of DNA sequencing and analysis of cancer cells not as widespread as one might expect?
Standard treatments and therapies for various types of cancer, including the nature of chemotherapeutic drugs, have improved significantly over the years. However, each cancer is different. Therefore, each person should receive treatment tailored to the abnormalities or mutations present in their diseased cells.
The cost of DNA sequencing and analysis has decreased significantly over the past decade. However, it’s still not as cheap as most people expect it to be. Therefore, genomic profiling of cancer is quite restricted, and the technology is available at only a handful of specialized research and cancer centers worldwide, including Dana-Farber, MSKCC, the Stanford Cancer Institute and the David H. Koch Institute for Integrative Cancer. Research at MIT.
To date, only a few patients have access to genomic sequencing of their cancer types. Therefore, only a select few can receive personalized medicine and targeted therapy.
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