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Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
Over the past few years, research in SLE has advanced profoundly and continues to advance as investigators in this field adopt new methodologies and new technology, many of which were mentioned in this chapter. Harnessing big data through GWAS and proteomics is a popular approach that has taken a front seat in translational research. Furthermore, the consideration of both innate and adaptive immunity in SLE has led to improved understanding of its pathophysiology and identification of new biomarkers that may be utilized as therapeutic targets in the future. A treat-to-target approach via targeted therapies has also become increasingly important. One example of such is the TARGET LUPUS research program (Targeting Disease, Agreeing Recommendations and Reducing Glucocorticoids through Effective Treatment in LUPUS), which was developed to encourage treatment trials and to reduce the use of glucocorticoids, which have been overused in this population for many years. So far, they have developed the glucocorticoid severity index in an effort to monitor glucocorticoid toxicity.96
Selected topics
Published in Henry J. Woodford, Essential Geriatrics, 2022
Targeted therapies interact with specific molecules to prevent the growth or spread of tumours. Examples include monoclonal antibodies directed against the human epidermal growth factor receptor 2 (HER2) for breast cancer, and tyrosine kinase inhibitors to block the growth of metastatic non-small cell lung cancer. Malignant cells have immune system evading mechanisms. Immunotherapies, such as checkpoint inhibitors, can be used to stimulate the immune system or counter immune-suppressing cancer actions. The physiological role of immune checkpoints is to prevent excessive immunity. This can be exploited by cancer cells to escape anti-tumour responses. Checkpoint inhibitors are effective for various malignancies, including some lung and metastatic cancers.36 These newer treatments tend to be tolerated better but do have the potential to cause systemic adverse effects. Chemotherapy-related cognitive impairment is possible and can persist for months to years after completion of treatment.37 It can affect a range of cognitive deficits. It has been detected in 35–60% of women following treatment for breast cancer but is usually only mild in severity. It is more common in older age and in people with pre-existing cognitive decline, making it important to assess cognition prior to chemotherapy. There are few published data on the effects of newer targeted therapies on cognition.
Molecular Drivers in Lung Adenocarcinoma: Therapeutic Implications
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Imayavaramban Lakshmanan, Apar Kishor Ganti
With increasing number of mutations being identified in NSCLC, the use of targeted agents against these pathways offers a promising therapeutic option. While it is possible that these agents will help NSCLC patients, the differential predictive ability of EGFR expression in lung, colorectal and squamous cell carcinoma of the head and neck serves as a cautionary tale. Patients found to have these molecular targets should be offered targeted therapies, but the optimal choice and timing of treatment is unclear.
GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer
Published in Expert Review of Precision Medicine and Drug Development, 2021
Amanda N. Lisby, John C. Flickinger, Babar Bashir, Megan Weindorfer, Sanjna Shelukar, Madison Crutcher, Adam E. Snook, Scott A. Waldman
The current lack of effective therapies and nonspecific cytotoxic limitations have led investigators to transition toward the development of predictive, preventative, and personalized medicine strategies to improve the treatment of CRC [1]. Targeted therapies, also referred to as precision medicine, interfere with cancer-specific molecules at a cellular level, working to slow or stop disease progression [13,14]. Rather than the generalized killing of replicating cells, targeted therapies are designed to selectively target unique biological features, exclusive to cancer cells, that inhibit growth, proliferation, or differentiation [15]. Precision therapy is characterized by treatment modalities tailored to target cancer-specific biomarkers [16]. Further, companion diagnostics are tools used to identify the population that will benefit from precision therapy, based on unique cancer-specific molecular characteristics, often by immunohistochemistry or next-generation sequencing [16]. While promising, only a few CRC-related pathways have been successfully exploited for CRC treatment – monoclonal antibodies targeting anti-epithelial growth factor (EGFR) and anti-vascular endothelial growth factor (VEGF) and most recently BRAF and HER-2 [17–22]. Furthermore, a small proportion of colorectal tumors harbor microsatellite instability (MSI) or deficient mismatch repair (dMMR) status, and respond well to treatment with checkpoint inhibitor-based immunotherapies [23–25].
Constructing a better binding peptide for drug delivery targeting the interleukin-4 receptor
Published in Journal of Drug Targeting, 2020
Xue-Di Bai, Xue-Wei Cao, Yi-Hui Chen, Long-Yun Fu, Jian Zhao, Fu-Jun Wang
Traditional antitumor drugs commonly used in clinical practice often have serious toxic and side effects on normal cells [1]. The emergence of targeted therapies has dramatically reduced the side effects of these drugs [2–4]. As mentioned in section ‘Introduction’, a number of targeted therapies that utilise common receptors (such as EGFR) have some limitations [5–10]. Using IL-4R as a target could effectively enrich the therapeutic sites for targeted-drug therapies and reduce the limitations of common receptors in different cells [6,11–13,20]. In this study, we selected IL-4R as the target and designed a new binding peptide, ILBP-ba, with better binding capacity. ILBP-ba has high selectivity and affinity for IL-4R high-expressing cells according to the results of the fluorescence experiment (Figure 4) and the competitive binding experiment (Figure 5). Our MTT assay showed that ILBP-ba significantly improved the toxicity of TCS to H226, A549 and HeLa cells (10.71, 12.63 and 13.99 folds, respectively), but there was no significant cytotoxicity improvement in SMMC cells (1.2-fold). This TCS toxicity improvement by ILBP-ba was positively correlated with IL-4R expression levels of four cells (Figure 6(B), Table 3). In addition, the apoptosis experiment showed that ILBP-ba only significantly enhanced the TCS-induced apoptosis in H226 cells, but not in SMMC cells (Figure 6(C)), consistent with the expression levels of IL-4R on both cell surfaces. Through the experiments above, we demonstrated that ILBP-ba is a high-selectivity and high-affinity targeted transport vector for IL-4R and is suitable for tumour-targeting therapy.
Pharmacovigilance of anti-cancer medicines: opportunities and challenges
Published in Expert Opinion on Drug Safety, 2020
Diana Crestan, Marta Paulina Trojniak, Sara Francescon, Giulia Fornasier, Paolo Baldo
In polypharmacy, pharmacodynamic and pharmacokinetic interactions can be dangerous to patients and may reduce the effectiveness of therapy. One drug (or natural product) can influence the metabolism of other compounds, by activating or inhibiting an enzyme, or modify the absorption of other drugs [42]. Molecularly targeted therapies induce a variety of individual pharmacogenetic responses, which may exacerbate drug-drug interactions. For example, the cellular uptake or metabolism of a drug may be affected by polymorphisms in the genes encoding transporters or metabolic enzymes, leading to differences in efficacy and toxicity in different patients [43]. Knowledge about the frequency of alleles for these polymorphisms in particular ethnic groups can be used by local health authorities to estimate the risk of ADRs and to take action to prevent them. For example, in Singapore, the frequency of polymorphisms inhibiting irinotecan metabolism, leading to neutropenia, was higher in persons of Indian descent than in other ethnic groups, leading health authorities to recommend that Indian patients receive lower doses of the drug [44].