Considerations for treatment duration in responders to immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have improved overall survival for cancer patients, however, optimal duration of ICI therapy has yet to be defined. Given ICIs were first used to treat patients with metastatic melanoma, a condition that at the time was incurable, little attention was initially paid to how much therapy would be needed for a durable response. As the early immunotherapy trials have matured past 10 years, a significant per cent of patients have demonstrated durable responses; it is now time to determine whether patients have been overtreated, and if durable remissions can still be achieved with less therapy, limiting the physical and financial toxicity associated with years of treatment.

PARP Inhibition in Cancer: An Update on Clinical Development.

PARP (poly(ADP-ribose) polymerase) inhibitors represent a novel class of anti-cancer therapy; they take advantage of synthetic lethality and induce cell death by exploiting a defect in DNA repair. This class of medication was initially evaluated in patients with BRCA-associated tumors, but efficacy was also demonstrated in other populations. Since 2014, four PARP inhibitors have been approved in various indications: olaparib, niraparib, and rucaparib in high-grade serous ovarian cancer, and olaparib and talazoparib in metastatic breast cancer.

Aldoxorubicin for the treatment of soft tissue sarcoma.

Intoduction: Soft tissue sarcomas (STS) encompass a group of rare tumors arising from mesenchymal tissue. Traditionally, anthracycline-based chemotherapy, with doxorubicin, is the main treatment for advanced STS. Areas covered: Aldoxorubicin is a doxorubicin derivative containing a carboxylic hydrazone and serves as a prodrug of doxorubicin.

Statins and pancreatic cancer.

Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer.

Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity.

Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle.

A Rare Finding of a BRAF Mutation in Renal Cell Carcinoma with Response to BRAF-Directed Targeted Therapy.

Whole exome sequencing can identify somatic mutations in malignant tumors and allow for personalized and novel treatment of common malignancies. Mutations in the BRAF gene are rare in renal cell carcinoma, and thus, BRAF inhibitors are not considered standard in the treatment of these cancers. Here, we report a case of a patient with a rare BRAF-mutated metastatic renal cell carcinoma who obtained a good clinical response to BRAF inhibition.

Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is an acute, stress-induced cardiomyopathy with an increased prevalence in post-menopausal women. The syndrome is most frequently precipitated by an acute emotional or physical stressor and mimics acute myocardial infarction with symptoms, electrocardiogram (ECG) changes and cardiac troponin elevation that are indistinguishable from those caused by plaque rupture or coronary thrombosis. Diagnosis of TTC is made when coronary angiography reveals no obstructive coronary artery disease and the left ventricle demonstrates apical ballooning and basal hypercontractility.

Adnectin-targeted inhibitors: rationale and results.

Adnectins are a family of binding proteins derived from the 10th type III domain of human fibronectin (10Fn3), which is part of the immunoglobulin superfamily and normally binds integrin. The 10Fn3 has the potential for broad therapeutic applications given its structural stability, ability to be manipulated, and its abundance in the human body. The most commonly studied adnectin is CT-322, which is an inhibitor of vascular endothelial growth factor receptor-2.

Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.

Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis.