Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027—a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

Revertant Mosaicism in Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of genetic blistering diseases characterized by mechanically fragile skin and mucocutaneous involvement. Historically, disease management has focused on supportive care. The development of new genetic, cellular, and recombinant protein therapies has shown promise, and this review summarizes a unique gene and cell therapy phenomenon termed revertant mosaicism (RM). RM is the spontaneous correction of a disease-causing mutation. It has been reported in most EB subtypes, some with relatively high frequency, and has been observed in both keratinocytes and fibroblasts. RM manifests as identifiable patches of unaffected, blister-resistant skin and can occur through a variety of molecular mechanisms, including true back mutation, intragenic crossover, mitotic gene conversion, and second-site mutation. RM cells represent a powerful autologous platform for therapy, and leveraging RM cells as a therapeutic substrate may avoid the inherent mutational risks of gene therapy/editing. However, further examination of the genomic integrity and long-term functionality of RM-derived cells, as well in vivo testing of systemic therapies with RM cells, is required to realize the full therapeutic promise of naturally occurring RM in EB.

Treatment with intralesional methotrexate injection in a patient with nail psoriasis

Psoriasis vulgaris is an inflammatory skin disease involving the skin, nails, and joints. While nail involvement is observed in 70–80% of patients with psoriasis, the rate of patients with isolated nail involvement is 5–10%. Dystrophies arising in the nails in psoriasis affect the patient’s quality of life, and local and systemic therapies may be used as treatment. Intralesional methotrexate or corticosteroid injection might be an option in the treatment of patients with the involvement of one nail or some nails or without the involvement of the skin and joints, due to the side effects of systemic and biological agents. Herein, we report a female patient with nail psoriasis resistant to a previously applied topical treatment, the efficacy of intralesional methotrexate without the use of a systemic antipsoriatic agent, and no progression of side effects.

NON SURGICAL TREATMENT OF CARCINOID LUNGS TUMORS

Typical carcinoid lungs tumors are neuroendocrine bronchopulmonary tumors with a low-grade malignancy, and an atypical carcinoid is an intermediate form of these tumors. Their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms. Currently, systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy.

Systemic Treatments for Adult Patients with Moderate-to-Severe Psoriasis: Consensus Statements for the United Arab Emirates

Background: Psoriasis is a chronic, immune-mediated disease characterized by mild localized plaques to severe plaques involving any part of the skin; it has a pronounced effect on patients’ quality of life. In the United Arab Emirates (UAE), there are limited local guidelines for the management of patients with psoriasis in daily clinical practice. Objectives: The study aimed to develop consensus statements for the evaluation and management of moderate-to-severe psoriasis in the UAE. Methods: To develop consensus statements, the Emirates Dermatology Society set up advisory board meetings in which local key opinion leaders (KOLs), including dermatologists from the UAE, participated. A targeted literature review was conducted to review current international and regional guidelines on the management of psoriasis, based on which the statements were formulated. A final consensus on each statement was reached based on collective agreement among the KOLs. Results : Consensus statements were generated with the intention of supporting physicians in clinical decision-making with respect to the classification of disease severity, treatment options including biologic and non-biologic systemic therapies, transitioning and adjusting of systemic therapies, and monitoring and management of psoriasis in special populations. Conclusion: These consensus statements could provide useful, practical guidance on the diagnosis and management of patients with moderate-to-severe psoriasis and would cater to the needs of physicians in the UAE.

An Overview of Intracranial Ependymomas in Adults

Ependymomas are rare primary central nervous system tumors. They can form anywhere along the neuraxis, but in adults, these tumors predominantly occur in the spine and less frequently intracranially. Ependymal tumors represent a heterogenous group of gliomas, and the WHO 2016 classification is based essentially on a grading system, with ependymomas classified as grade I, II (classic), or III (anaplastic). In adults, surgery is the primary initial treatment, while radiotherapy is employed as an adjuvant treatment in some cases of grade II and in all cases of anaplastic ependymoma; chemotherapy is reserved for recurrent cases. In recent years, important and interesting advances in the molecular characterization of ependymomas have been made, allowing for the identification of nine molecular subgroups of ependymal tumors and moving toward subgroup-specific patients with improved risk stratification for treatment-decisions and future prospective trials. New targeted agents or immunotherapies for ependymoma patients are being explored for recurrent disease. This review summarizes recent molecular advances in the diagnosis and treatment of intracranial ependymomas including surgery, radiation therapy and systemic therapies.