When it comes to medicine, it is a most satisfying time to be alive because development in genomic science presents us with the opportunity of being able to design a treatment for each and every one of the patients. The concept relating to this is called personalized or precision medicine which, when applied to level of genomic pathology whereby genetic data is integrated to make the diagnosis, prognosis and therapy of oncology, rare disease and other conditions, is the most powerful.
Healthcare professionals who integrate genomic information into their clinical practices are able to not only advocate for a suitable treatment plan such as recommending a therapy that is best suited for the patient but also avoid adverse effects, hence making the optimum use of available resources.

In this article, we pursue the integration of genomic information in the management of patients as part of personalized medicine through genomic pathology, genetic testing and molecular profiling also in the flow of work.

Genomic Pathology: Understanding the Basics

It is important to build a strong base of understanding the general definition of genomic pathology first, before explaining its basic aspects. Genomic pathology, in its most basic definition, is the application of scientific knowledge that employs both genetic and molecular studies in order to understand the disease, especially cancer, on genetic basis. A patient’s disease can be characterized by looking at mutations, patterns of gene expression, genomic variety, and other genomic abnormalities. This makes it possible to determine the molecular pathways causing the problem. By doing so, the information aids in the formulation of treatment plans, timeliness of the problem, and the presence or absence of the problem.

One of the focuses of genomic pathology in personalised medicine can be outlined as follows:

1. Genetic Mutations: Changes in the order of DNA that have potential to promote disease events.
2. Gene Expression Profiling: Identifying the location of active or inactive genes within a specimen of tissue which constitutes an insight into the reproductive sicknesses.
3. Genetic Susceptibility: Mutations in the genomes of the patients that would increase their chances of acquiring particular conditions or their response to the pharmacological agents.
4. Somatic versus Germline Mutations: They identify the inherited genetic alterations (germline) and genetic changes that occur in the identity of a person (somatic) over the time and has its bearing on the treatment approaches.

Genomic Pathology in Cancer: A Major Focus Area

One of the areas that has registered significant success is through the application of genomic pathology in oncologic studies because it has changed the management of cancer. The bronchodilators, chemotherapy and radiotherapy that are employed are classic in nature and mostly uniform for different patients, hence their efficiency may be low and they may also have escalating complications. However, because of the genomic profiling, a specificity is acquired.

Targeted Therapies and Cancer Precision Medicine Genomic analysis of tumor specimens demonstrates mutations or alterations in cancer growth genes such as EGFR, which stands for epidermal growth factor receptor, BRAF, KRAS, and HER2, among others. Such findings make it possible to take advantage of targeted therapies which are drugs developed to interrupt the cancer via the specific molecular modifications that characterize the disease. For instance, in non-small cell lung cancer (NSLSC), patients with EGFR-positive tumors may use EGFR inhibitors like erlotinib or gefitinib that block mutant gene products and thus, the tumor. Overexpressed HER2 forty percent in breast cancer, the patient can benefit from trastuzumab (Herceptin) that specifically targets HER2-positive cancer cells.

Next-Generation Sequencing (NGS) NeXT generation sequencing allows one to evaluate the overly complex genetic structure of a tumor in a single test which identifies more comprehensive pictures of mutations and alterations causing cancer aggressiveness. This system is much more efficient than previous protocols like a series of single-gene tests and multi genetic changes can be identified in an instance.
So why is NGS relevant in oncology when looking at, particularly aggressive tumors such as melanoma, a BRAF mutant tumor, where BRAF directing inhibitors such as vemurafenib may be promising? As already mentioned, NGS assists not only in detecting the MSH6 alterations but also in MSI or TMB status which may predict response to immunotherapy including checkpoint blockade.

Therapeutic Drug Monitoring: Patient-Specific Care

Therapeutic drug monitoring is considered one of the branches of clinical pharmacology and genomics that studies the influence that the characteristics of a person carry over the effects of medications. The differences in these genes include polymorphisms in genes coding for drug metabolizing enzymes and variants in transporter proteins that determine whether a sequence is likely to cause side effects or be beneficial.

In genomic therapeutics, pharmacogenomic studies are conducted to determine which drugs are best for specific patients. For example:

1. A polymorphous CYP450 gene family is essential for drug metabolism and their polymorphisms explain why a patient is able to metabolize warfarin, clopidogrel or tamoxifen.
2. In cancer, TP53 (as the tumor suppressor gene) or BRCA1/BRCA2 e.g. breast cancer predisposition genes mutations may affect the therapeutic decisions including the use of PARP inhibitors or platinum-based drugs.

There say genomic pharmacogenomics testing can reduce prescription failures where drugs integrated in the treatment do not help, prevent adverse drug effects, and enhance patient’s prognosis overall.

Genomic Pathology in Rare Diseases For more than oncology, genomic pathology also plays an essential part in the detection and therapy of rare genetic disorders. Many genetic rare disease forms are caused by almost always a single gene mutation that ultimately produces a definitive clinical phenotype. The development of genome technology has made it possible to explain these diseases’ genetic backgrounds even if genetic evidence is not readily visible within the clinical presentation. For example, rare inherited diseases such as cystic fibrosis, muscular dystrophy, and Huntington’s disease have specific inheritance patterns that allow for genetic testing to confirm the diagnosis and guide clinical management. There are also ongoing investigations of gene therapy methods that target and repair defective genes for sickle- cell disease and beta-thalassemia.

Dr. AKanksha Awasthi 

Ethics in Genomic Medicine

In contrast to these vast opportunities, genomic medicine represents a number of considerable ethical and factual issues which include:

1. Structural Violence: Economic barriers are likely to limit the access that many people have to genomic testing and even genomic individualized therapies, inducing healthcare inequities.
2. Clinical Relevance: There are limited places in the medical literature that explain the pathogenicity of genetic variations and separating disease-modifying mutations from innocuous polymorphisms is often challenging.
3. Real Cost: Advanced genomic tests and personalized therapy options may be expensive, paying for advanced diagnostic tools may not always be endorsed by the reimbursement policy.

Conclusion

Genomic pathology has revolutionized personalized medicine by reconstructing diseases’ genetic architecture at the molecular level. In the field of oncology, it assists to find relevant pre-certified molecules, which substantially improve the therapeutic outcome, whereas in pharmacogenetics, it directly aids in the optimization of pharmacotherapy with minimal side effects and maximal effectiveness. New possibilities for the application of genomic technology offer new prospects for the rapid diagnosis and successful treatment of rare diseases and previously undiagnosed disorders.

References

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