scholarly journals Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency

2021 ◽  
Vol 11 (11) ◽  
pp. 1186
Author(s):  
Gyrid Nygaard ◽  
Peter D. Szigetvari ◽  
Ann Kari Grindheim ◽  
Peter Ruoff ◽  
Aurora Martinez ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Status ◽  
Dopamine Synthesis ◽  
Hydroxylase Deficiency ◽  
Catecholamine Biosynthesis ◽  
Improve Treatment ◽  
Key Enzyme ◽  
Gch1 Gene

Dopa-responsive dystonia (DRD) is a rare movement disorder associated with defective dopamine synthesis. This impairment may be due to the fact of a deficiency in GTP cyclohydrolase I (GTPCHI, GCH1 gene), sepiapterin reductase (SR), tyrosine hydroxylase (TH), or 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) enzyme functions. Mutations in GCH1 are most frequent, whereas fewer cases have been reported for individual SR-, PTP synthase-, and TH deficiencies. Although termed DRD, a subset of patients responds poorly to L-DOPA. As this is regularly observed in severe cases of TH deficiency (THD), there is an urgent demand for more adequate or personalized treatment options. TH is a key enzyme that catalyzes the rate-limiting step in catecholamine biosynthesis, and THD patients often present with complex and variable phenotypes, which results in frequent misdiagnosis and lack of appropriate treatment. In this expert opinion review, we focus on THD pathophysiology and ongoing efforts to develop novel therapeutics for this rare disorder. We also describe how different modeling approaches can be used to improve genotype to phenotype predictions and to develop in silico testing of treatment strategies. We further discuss the current status of mathematical modeling of catecholamine synthesis and how such models can be used together with biochemical data to improve treatment of DRD patients.

New Options and New Questions: How to Select and Sequence Therapies for Patients with Metastatic Melanoma

2012 ◽  
pp. 524-530 ◽  
Author(s):  
Keith T. Flaherty ◽  
Jeff A. Sosman ◽  
Michael B. Atkins
Keyword(s):  
Tumor Immunology ◽  
Immune Checkpoint Inhibitor ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Braf Inhibitor ◽  
Current Status ◽  
Molecularly Targeted Agents ◽  
New Treatment ◽  
Braf Mutant ◽  
Selection Of

Overview: Recent advances in the understanding of the melanoma biology and tumor immunology have yielded new treatment strategies for patients with advanced melanoma. Within the past year, the selective BRAF inhibitor vemurafenib and immune checkpoint inhibitor ipilimumab have been added to the treatment armamentarium. In addition, other molecularly targeted agents and immunotherapies are showing considerable promise. The availability of multiple, effective treatment options for patients with melanoma, although long sought, has complicated treatment decisions. This article will review the advances in our understanding of melanoma biology and tumor immunology, the current status of immunotherapy, the advances in molecularly targeted therapy for patients with BRAF mutant melanomas, the possible approaches to patients with BRAF wild-type (WT) tumors, and the current considerations for treatment selection of individual patients.

scholarly journals Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Brain ◽  
2010 ◽  
Vol 133 (6) ◽  
pp. 1810-1822 ◽  
Author(s):  
M. A. Willemsen ◽  
M. M. Verbeek ◽  
E.-J. Kamsteeg ◽  
J. F. de Rijk-van Andel ◽  
A. Aeby ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Hydroxylase Deficiency ◽  
Catecholamine Biosynthesis ◽  
Tyrosine Hydroxylase Deficiency

scholarly journals Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5722
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Andreas Hochhaus ◽  
Sebastian Scholl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Epigenetic Therapy ◽  
Comprehensive Overview ◽  
Secondary Resistance ◽  
Acute Myeloid

Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients.

scholarly journals Evolving treatment strategies of brain metastases from breast cancer: current status and future direction

2020 ◽  
Vol 12 ◽  
pp. 175883592093611 ◽  
Author(s):  
Jae Sik Kim ◽  
In Ah Kim
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Tumor Biology ◽  
Local Treatment ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Antitumor Effects ◽  
Systemic Treatments

Remarkable progress in breast cancer treatment has improved patient survival, resulting in an increased incidence of brain metastasis (BM). Current treatment options for BM are limited and are generally used for palliative purposes. Historically, local treatment, consisting of radiotherapy and surgery, is the standard of care due to delivery limitations of systemic treatments through the blood–brain barrier. However, as novel biological mechanisms for tumors and BM have been discovered, several innovative systemic agents, such as small-molecular-targeted therapy and immunotherapy, have begun to change the treatment paradigm. In addition, efforts to maximize antitumor effects have been attempted using combination therapy, informed by tumor biology. In this comprehensive review, we will highlight various clinical trials investigating the treatment of BM in breast cancer patients, discuss presently available treatment options, and suggest potential directions of future therapeutic targets.

Using Naïve Bayes Algorithm to Estimate the Response to Drug in Lung Cancer Patients

2019 ◽  
Vol 21 (10) ◽  
pp. 734-748 ◽  
Author(s):  
Baoling Guo ◽  
Qiuxiang Zheng
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Drug Response ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Cancer Resistance ◽  
Lung Cancer Patients ◽  
Bayes Algorithm

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.

Treatment Strategies Against Diabetic Foot Ulcer: Success so far and Road Ahead

2020 ◽  
Vol 16 ◽  
Author(s):  
Ankit Awasthi ◽  
Sachin Kumar Singh ◽  
Bimlesh Kumar ◽  
Monica Gulati ◽  
Rajesh Kumar ◽  
...  
Keyword(s):  
Lower Limb ◽  
Diabetic Foot ◽  
Treatment Strategies ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Arterial Disease ◽  
Current Status ◽  
Limb Amputation ◽  
Bibliographic Databases ◽  
Inflammatory Phase

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It isassociated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. Basically, there are four stages of wound healing namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Traditionally the dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer from many years. Introduction: In this review the global prevalence as well as etiopathogenesis related to diabetic foot ulcer has been discussed. Potential role of various synthetic and herbal drugs as well as their conventional dosage form for the effective management of diabetes foot ulcer has been highlighted. Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of various approaches that are used for the treatment of diabetic foot ulcer. Results: About 142 papers including both, research and review articles, were included in this review in order to produce a comprehensive as well as readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action. Conclusion: DFU has become one of the most common complications in patients having more than ten years of diabetes. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as judicious selection of drug as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemics or, they have been repositioned. Moreover, in clinical practice, much focus has been given towards dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that a combination therapy of herbal and synthetic drug with multiple treatment pathway could be able to overcome the disease.

scholarly journals Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Future Directions ◽  
Sequencing Technologies ◽  
E6 And E7 ◽  
The Continuum

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

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