Pharmacogenetics for severe adverse drug reactions induced by molecular‐targeted therapy

Udagawa, Chihiro; Zembutsu, Hitoshi

doi:10.1111/cas.14609

Cited by 14 publications

(13 citation statements)

References 72 publications

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“…Molecular-targeted drugs may interfere with molecules that are overexpressed in target cancer cells. These drugs may cause life-threatening ADRs which deserve particular PGx attention [11,124].…”

Section: Cancermentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

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Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug–drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

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Section: Cancermentioning

confidence: 99%

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Cacabelos

Naidoo

Corzo

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…However, despite these findings, the pathogenic role of the IL-17 pathway in primary and ICI-induced pituitary (and hypothalamic) dysfunction needs to be better clarified. Finally, a potential role of some gene polymorphisms in prompting ICI-related toxicity has been suggested [ 6 , 65 ]. Some CTLA-4 polymorphisms are commonly associated with autoimmune disorders, including endocrinopathies (i.e., T1DM, Graves’ disease, autoimmune hypothyroidism, and Addison’s disease) [ 6 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…Only in a few studies has a linkage between PD-1 polymorphisms and T1DM has been suggested, while PD-L1 polymorphisms were found to be linked to T1DM, Graves’ disease, and Addison’s disease [ 6 , 66 ]. Based on these data and the well-documented association between some germline genetic variants and adverse events induced by anticancer agents [ 67 ], an association between specific gene polymorphisms of immune checkpoints and the development of ICI-induced toxicities has been postulated [ 6 , 65 ]. However, studies on the role of gene polymorphism in ICI-induced hypothalamic–pituitary dysfunction are needed.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle

Barnabei

Corsello

Paragliola

et al. 2022

Cancers

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Immune checkpoint inhibitors (ICI) prolong the survival in an increasing number of patients affected by several malignancies, but at the cost of new toxicities related to their mechanisms of action, autoimmunity. Endocrine toxicity frequently occurs in patients on ICI, but endocrine dysfunctions differ based on the ICI-subclass, as follows: agents targeting the CTLA4-receptor often induce hypophysitis and rarely thyroid dysfunction, which is the opposite for agents targeting the PD-1/PD-L1 axis. Recently, few cases of central diabetes insipidus have been reported as an adverse event induced by both ICI-subclasses, either in the context of anterior hypophysitis or as selective damage to the posterior pituitary or in the context of hypothalamitis. These new occurrences demonstrate, for the first time, that ICI-induced autoimmunity may involve any tract of the hypothalamic–pituitary axis. However, the related pathogenic mechanisms remain to be fully elucidated. Similarly, the data explaining the endocrine system susceptibility to primary and ICI-induced autoimmunity are still scarce. Since ICI clinical indications are expected to expand in the near future, ICI-induced autoimmunity to the hypothalamic–pituitary axis presents as a unique in vivo model that could help to clarify the pathogenic mechanisms underlying both the dysfunction induced by ICI to the hypothalamus–pituitary axis and primary autoimmune diseases affecting the same axis.

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“…This may be done with the use of small molecules, monoclonal antibodies, therapeutic cancer vaccines, or gene therapy which function to ultimately promote cell death (16). Molecular targeted therapy rarely produces adverse side effects due to its personalization towards the patients' genetic profile (17). Patients may benefit from a combination of chemotherapy and molecular targeted therapy and increase the effectiveness of treatment.…”

Section: Molecular Targeted Therapymentioning

confidence: 99%

The Influence of Analgesic Modalities on Postoperative Cancer Recurrence

et al. 2022

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: The potential for cancer cells to grow and to metastasize depends on complex interactions between inflammatory signals and pathways, immune cells, and elements of the stromal tissue in which they invade. Related to the nature of many cancers, the probability of recurrence can potentially be quite high for some patients. Immunology, lifestyle modifications, timing of disease, genetics, age, gender, and race are only a handful of ways the likelihood of cancer recurrence can be influenced. The quantity, or density, of certain immunological cells or factors, plays a role in the propagation of cancer cells. Opioids are often used in cancer patients for acute postoperative and chronic pain management. While they can produce significant pain relief, the type of analgesic utilized is important, as it may influence cancer propagation. In this regard, certain opioids have been found to increase T regulatory cells while suppressing NK cell function. Morphine may promote tumor neovascularization and expansion. Fentanyl administration significantly diminishes NK-cells and CD8+ cytotoxic T-cells. In a recent meta-analysis, propofol-based anesthesia improved both cancer-free survival and overall survival. COX inhibitors have also shown promise in persevering cancer immune function, as in literature involving ketorolac and celecoxib. In summary, inhaled anesthesia and opioids may contribute to a pro-tumor metastasis environment also known as cancer propagation; whereas propofol and COX inhibitors may provide a better alternative to reduce cancer recurrence and propagation.

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Pharmacogenetics for severe adverse drug reactions induced by molecular‐targeted therapy

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 14 publications

References 72 publications

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions

Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle

The Influence of Analgesic Modalities on Postoperative Cancer Recurrence

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