Table of Contents
- DNA Sequencing For Cancer Treatment
- 1. Determining the presence of specific known mutations in a sample for personalized cancer treatment
- 2. Demystifying the development of resistance to treatment /medicine in post-treatment cancer cells
- 3. Identifying genomic biomarkers and predicting the efficiency of immunotherapy for specific cancer types
- Why is the impact of DNA sequencing and analysis of cancer cells not as wide-ranging as one expects it to be?
Cancer is caused by changes in the DNA – genetic material that controls the cell function. In most cases, cancer is the result of uncontrolled cell division due to abnormalities in the DNA. Some of these changes can be inherited, but some can be sporadic.
Each type of cancer can have a unique set of genetic mutations. The specific changes in the 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.
The DNA sequencing and analysis of a sample from the tumor of a patient entails determining the arrangement of the four bases– A, T, G, and C. Human cells contain around 6 billion bases, which are roughly 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 a sample for personalized cancer treatment
Every genetic abnormality does not result in cancer. However, particular mutations can be hallmarks of specific cancer types. For example, the mutations in the EGFR gene is present in several non-small cell lung cancer (NSCLC). Today, a group of drugs is available that counter the effects of the EGFR gene mutation selectively. Therefore, anyone diagnosed with NSCLC can get their tumor DNA sequenced to check if they have EGFR mutation so they can benefit from the particular treatment.
At elite cancer research and treatment centers like 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 typically linked 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 therapies as parts of clinical trials. For example, as a part of new research at Memorial Sloan Kettering Cancer Center (MSKCC), the scientists discovered that 37% of the samples among over 10,000 tumor biopsies had one or more mutations that could be addressed with existing therapies and medication.
2. Demystifying the development of resistance to treatment /medicine in post-treatment cancer cells
At the same time, large-scale sequencing projects like The Cancer Genome Atlas (TCGA) have data from thousands of whole-exome sequencing (WES) reactions. Comparative studies involving data from the TCGA can be used to track how cancers gradually change their genetic stripes.
Additionally, sequence comparison data from tumors before and after treatment can offer the healthcare professionals and researchers an understanding of the mechanism(s) by which certain types of cancers become resistant to treatment. Elucidating the mechanism of resistance to therapy in specific cancers can help researchers determine alternative and more effective courses of treatment.
For example, researchers at the Center for Prevention of Progression of Blood Cancer at Dana Farber collect tissue samples from individuals with precursor conditions that potentially develop into multiple myeloma and other hematological cancers. Genetic sequencing of these samples can help the researchers understand the evolution of these diseases and develop drugs that can stop disease progression in the earliest possible stages.
Also, read about What is Blood Cancer Symptoms, Causes, Types and Treatment
3. Identifying genomic biomarkers and predicting the efficiency of immunotherapy for specific cancer types
Several studies have shown the possibility of treating several types of cancer using checkpoint inhibitors in the human immune system. Immunotherapy is especially useful in the treatment of pre-treated and recurrent cancer variants. These studies identify the genomic biomarkers and their variants in healthy vs. cancer cells.
For example, the over-activation of the anti-PD-1/PF-1 genes is found in specific types of cancers like lymphoma. On the other hand, lung cancer, melanoma, and MSI-positive colorectal cancer exhibit a high mutation load across the entire genome. The treatment of different cancer types using immunotherapy shows varying levels of efficacy.
Mutations of the HLA presentations and INF-gamma pathway is often related to resistance to immunotherapy. WES and Whole Genome Sequencing (WGS) elucidate the DNA sequences within the cancer cells that are vulnerable to immunotherapy. The new-age DNA sequencing and analysis techniques elucidate the neoantigen signatures and the quality and quantity of immune cells from tumor specimens (pre-treated and post-treated) as well as the immune cells used in immunotherapy.
Why is the impact of DNA sequencing and analysis of cancer cells not as wide-ranging as one expects it to be?
Standard therapies and treatments for different types of cancer, including the nature of chemotherapeutic drugs, have improved over the last few years significantly. Nonetheless, each cancer is different. Therefore, every person should receive a treatment tailored for the abnormalities or mutations that are present in his or her diseased cells.
The cost of DNA sequencing and analysis has come down significantly in the past decade. However, it is still not as affordable as most people expect it to be. Therefore, the genomic profiling of cancer is quite restricted, and the technology remains available at only a handful few elite research and cancer centers across the world, including Dana-Farber, MSKCC, Stanford Cancer Institute, and 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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