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Overview of Therapeutic Biomarkers in Cancer
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Sherry X. Yang, Janet E. Dancey Treatment
The advances in cancer genetics and biology have unveiled many key molecular or genetic alterations that play critical roles in cancer pathogenesis, and in driving tumor growth and progression. The genomic or genetic aberrations are the basis of targeted cancer therapy. Drugs that are developed to target the molecular mechanisms of cancer with defined biological functions are referred to as targeted cancer therapeutics [21]. This class of drugs block the growth and metastasis of cancer by interfering with the molecular targets or genetic abnormalities [21]. In the past two decades particularly last 10 years, the number of targeted agents approved for clinical use has increased compared to cytotoxic chemotherapy, with many more in pre-clinical, and early and late stages of clinical development. The targeted therapeutics include small-molecule drugs and biologics, which includes monoclonal antibodies, drug-antibody conjugates, vaccines, recombinant therapeutic proteins, immune checkpoint inhibitors, tumor vaccines, and, recently, chimeric antigen receptor (CAR) T cells for gene and targeted therapy [22].
Branching out: Specialties and subspecialties in medical genetics
Published in Peter S. Harper, The Evolution of Medical Genetics, 2019
Alongside the increased demand for cancer genetics services, and to a considerable extent responsible for it, has been a major change in the public and professional perception of the nature of cancer generally. Although a genetic predisposition was widely recognised in the nineteenth and the first part of the twentieth century, cancer later became generally considered by the population at large to be largely environmental in its causes, with factors such as diet and viruses the main focus. Now, however, with the publicity given to gene discoveries, the main basis is felt to be ‘genetic’, despite the fact that specific genes in the germ line giving a high risk to relatives are only involved in a small minority of cases, most mutations being purely somatic. It is interesting to contrast this change in perception with some other disorders such as peptic ulcer, formerly considered mainly genetic and the subject of long chapters in genetics textbooks, where the genetic aspects have become of less interest now that specific external factors have been recognised.
Precision medicine for colorectal cancer
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Candan Hızel, Şükrü Tüzmen, Arsalan Amirfallah, Gizem Çalıbaşı Koçal, Duygu Abbasoğlu, Haluk Onat, Yeşim Yıldırım, Yasemin Baskın
This section focuses on the technologies underlying high-throughput genomics for detecting potential genomic alterations as risk evaluation for CRC. Additionally, it inspects the preliminary results of next-generation genome sequencing analysis of CRC genomes for personalized medicine and microarrays for diagnostic and treatment selection in CRC, and reviews the challenges met in the discovery phase of new genetic aberrations. Since the completion of the Human Genome Project, the appearance of the scientific age of “omics” has transformed the cancer research. The International Cancer Genome Consortium (ICGC) is synchronizing scientific research targeted at discovering genomic modifications that are linked to cancer (Tran et al., 2012; Sikdar et al., 2016; ICGC International Data Access Committee, 2016). Discoveries along these lines greatly depend on the development of novel tools in molecular diagnostics, especially in the area of whole genome sequencing. The enhanced timelines and cost-effective technologies have expedited discovery in cancer genomics as well as in translational medicine (Tran et al., 2012). Nevertheless, challenges still exist prior to PCM becoming available for the population at large on an everyday bases.
A brief review of the current knowledge on environmental toxicants and risk of pediatric cancers
Published in Pediatric Hematology and Oncology, 2022
Omar Shakeel, Philip J. Lupo, Simon Strong, Manish Arora, Michael E. Scheurer
Each year in the United States, more than 15,000 children and adolescents are diagnosed with cancer, which is the leading cause of disease-related mortality among youth.1 Notably, the incidence of pediatric cancers has steadily increased (approximately 0.8% per year) since 1975, resulting in a 45% increase between 1975 and 2018 (https://seer.cancer.gov/explorer/). Through large-scale sequencing efforts, we now know that approximately 10% of all cancers in children are caused by an inherited pathogenic variant.2 Additionally, recent advances in cancer genetics have led to a better understanding and improved molecular classification of some of these cancers, which has led to improved survival in some instances. However, for most children, the underlying etiologies of their cancers remain largely unknown, suggesting that exogenous factors are accounting for an increasing proportion of cases.1
A wide perspective of targeted therapies for precision medicine in autoimmune diseases
Published in Expert Review of Precision Medicine and Drug Development, 2020
Ippei Miyagawa, Satoshi Kubo, Yoshiya Tanaka
In 2015, Barack Obama, the then President of the United States of America, stated that the government had begun to promote state-driven precision medicine [1]. The strategy of precision medicine involves the stratification of patients to improve diagnosis and medical treatment. In brief, the therapeutic target is narrowed by stratifying patients with a single disease. For example, patients with Epidermal Growth Factor Receptor (EGFR)-mutated non-small-lung cancer had remarkably better outcomes following treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs) than following treatment with other conventional anticancer agents [2]. Namely, the therapeutic effect of EGFR TKIs in patients with EGFR mutations was higher than that of the conventional one-size-fits-all strategy for all patients with non-small-cell lung cancer. This representative example shows that precision medicine has a strong therapeutic effect. Thus, precision medicine currently offers the most effective treatment for patients with malignant tumors and is based on the development of targeted therapies using cancer genomics. In other words, precision medicine is achieved by two factors: the stratification of patients and the use of targeted therapies that specifically suppress a single agent or multiple therapeutic targets. When both factors work, patients are likely to have good outcomes.
How can bioinformatics contribute to the routine application of personalized precision medicine?
Published in Expert Review of Precision Medicine and Drug Development, 2020
Carlos Carretero-Puche, Santiago García-Martín, Rocío García-Carbonero, Gonzalo Gómez-López, Fátima Al-Shahrour
It is important to highlight the key role of data sharing initiatives for PPM implementation. For instance, cancer PPM is currently hampered by the lack of complete clinical and histopathological records in the cancer genomics public databases. In this context, data sharing arises as a rational alternative toward more comprehensive data sources and subsequently more accurate tools. In addition, the possibility of expanding the availability of health-related data through extensive digitization of medical records and collaboration among countries for the secure exchange of such data will represent a paradigm shift not only for policymakers and biomedical scientists, but also for citizens. Accordingly, a number of regulatory frameworks and proposals to establish legal margins to access human genetic and phenotypic data avoiding health inequities in PPM-based initiatives are taking their first steps [7]. In this sense, the establishment of solidarity-based legal frameworks will be also key in data sharing across health care systems while fundamental rights are respected and data privacy and security are guaranteed [8].