ABSTRACT
The management of cancer has been traditionally dependent on the primary tumour type and specific histologic subtypes. Recently, the introduction of molecular profiling tools and its increasing use in clinical practice has facilitated the emergence of novel genomically driven treatment options within the standard of care landscape as well as in the clinical trial setting. One such aberration is mutation in v-Raf murine sarcoma viral oncogene homolog B (BRAF), which results in hyperactivation of RAS-RAF-MEK-ERK signaling in the Mitogen-activated protein kinases (MAPK) pathway. BRAF and Mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK) inhibitors, although being currently approved for melanoma, non-small cell lung cancer (NSCLC) and colon cancer, have reported activity across other various cancers harbouring BRAF aberrations. It has been proposed that combined MEK and BRAF inhibition could overcome the acquired resistance commonly developed among patients receiving BRAF or MEK inhibitors as monotherapy. We report five cases of BRAF V600E (substitution of glutamic acid for valine in codon 600) aberrant refractory metastatic cancers treated with dual BRAF/MEK combination inhibitor therapy leading to an excellent clinical and radiological response and protracted duration of disease control.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Neoplasms/drug therapy , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Female , Humans , Male , Middle Aged , Mitogen-Activated Protein Kinase Kinases/metabolism , Mutation , Neoplasms/genetics , Neoplasms/pathology , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins B-raf/genetics , Treatment OutcomeABSTRACT
As research focus in oncology has recently shifted from oral targeted therapy to immunomodulation, the era of successful drug development in bladder cancer has just begun. This has led to unprecedented approval of five immunotherapeutic agents by regulatory agencies for metastatic bladder cancer within a span of 12 months. With an initial triumph of anti-programmed cell death-1 (anti-PD-1) and anti-programmed cell death ligand-1 (anti-PDL-1) drugs, ongoing efforts are aimed at identification and validation of new druggable immune targets to consolidate the initial gains. In this paper, we review the role of immunotherapy in the treatment of bladder cancer as well as the various emerging immunotherapeutic agents and their possible use in bladder cancer.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Molecular Targeted Therapy , Neoplasm Proteins/immunology , Urinary Bladder Neoplasms/therapy , Animals , Humans , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/metabolismSubject(s)
Breast Neoplasms , Complementary Therapies , Drug Therapy , Mastectomy , Neoplasms, Multiple Primary , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Clinical Decision-Making , Complementary Therapies/methods , Complementary Therapies/psychology , Drug Therapy/methods , Drug Therapy/psychology , Female , Humans , Mastectomy/methods , Mastectomy/psychology , Middle Aged , Neoplasm Staging , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/pathology , Patient Preference , Physician-Patient Relations , Treatment Refusal/psychologyABSTRACT
BACKGROUND: Behçet's disease is a progressive diffuse inflammatory vasculitis characterized by recurrent oral and genital ulceration and ocular inflammation. Cardiac involvement is a rare but well-documented manifestation of Behçet's disease. Complete heart block in non-Caucasian populations has been reported previously; however, in this report, we describe a unique case of complete heart block in a Caucasian woman with Behçet's disease. CASE PRESENTATION: A 48-year-old Caucasian woman presented to our hospital with symptomatic complete heart block requiring a pacemaker implant on a background of recurrent oral and genital ulcers and oligoarthritis of 10 months' duration. She also had a history of recurrent diarrhea with a single episode of ocular inflammation in the recent past. She had no evidence of cardiac ischemia, and her autoimmune antibodies were within normal ranges. She was diagnosed with Behçet's disease according to international study group criteria and was commenced on prednisolone and sulfasalazine, to which she responded very well. CONCLUSIONS: Cardiac complications should be considered when making a diagnosis of Behçet's disease, even in Caucasian patients. While mucocutaneous ulceration is indeed the most common manifestation of Behçet's disease, cardiovascular involvement tends to cause the most morbidity and mortality.
