Sacituzumab govitecan is an antibody-drug conjugate. It is composed of a humanized monoclonal antibody raised against the trophoblast cell-surface antigen 2 (Trop-2), and linked to SN-38, which is an active metabolite of topoisomerase I inhibitor anticancer drug irinotecan. A hydrolyzable linker conjugates the antibody and the drug. Trop-2 is overexpressed in various tumors including the triple-negative breast cancers (TNBCs) that are more aggressive with limited therapeutic options. Sacituzumab govitecan has proven to be an important therapeutic modality to manage the TNBCs. It has shown progression-free survival (PFS) and overall survival (OS) benefits when compared to standard-of-care chemotherapeutics. Accordingly, it is approved for the treatment of TNBCs in the United States and the European Union. Sacituzumab govitecan has also shown PFS and OS benefits for hormone receptor-positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancers. Therefore, sacituzumab govitecan appears to be an option for HR+/HER2- metastatic breast cancers that are heavily pretreated and exhibit endocrine resistance. Although sacituzumab govitecan has shown promise, it also is toxic. Additional studies are therefore needed to further refine the use of sacituzumab govitecan in improving the management of metastatic breast cancer.
The cyclin-dependent kinase (CDK) inhibitors have emerged as important cancer therapeutics. To date, three CDK4/6 inhibitors in combination with endocrine therapy have been approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive, HER2-negative advanced breast cancer. These include, palbociclib, ribociclib and abemaciclib. More recently, a newer CDK4/6 inhibitor named dalpiciclib has been tested in the phase III DAWNA-1 study, which is a randomized, double-blind, placebo-controlled trial that investigates dalpiciclib in combination with fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer patients that have relapsed or progressed on prior endocrine therapy. Dalpiciclib is an oral agent and an emerging ATP-competitive CDK4/6 inhibitor. The interim results of DAWNA-1 study revealed that dalpiciclib in combination with fulvestrant significantly prolonged the progression-free survival. The clinical use and side effects of palbociclib, ribociclib and abemaciclib as well as dalpiciclib are reviewed here.
800x600 Pembrolizumab is an immune checkpoint inhibitor antibody. It is a humanized monoclonal antibody directed against cytotoxic T cell immune checkpoint receptor named programmed death 1 (PD-1) (1, 2). PD1 is believed to transduce inhibitory signals when bound to its ligand PD-L1 or PD-L2 (1, 2). Pembrolizumab when bound to PD1 is believed to block PD1 interactions with PD-L1/PD-L2 and consequently enhances cytotoxic T cell effects on tumor cells (1, 2). In a recent article, Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";}
Protein kinase D (PKD) belongs to a family of serine/threonine kinases in the calcium/calmodulin-dependent kinase superfamily. It modulates a number of signal transduction pathways involved in regulation of cell proliferation, survival, migration, angiogenesis, regulation of gene expression, and protein/membrane trafficking, mediated by variety of stimuli such as growth factors, hormones, and cellular stresses. Although its role in cancer progression remains elusive, current literature supports a potential tumor promoting function of the selective PKD isoforms in prostate cancer, making them promising therapeutic targets for cancer treatment.
Anaplastic lymphoma kinase (ALK) gene is present on chromosome 2. ALK gene locus undergoes inversion leading to echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK gene fusion resulting in an oncogenic fusion protein. The ALK abnormality occurs in ~3-7% of non-small cell lung carcinoma (NSCLC) and generally associates with adenocarcinoma in those who never smoked or smoked occasionally. Crizotinib (Xalkori) was the first ALK inhibitor approved by the FDA in 2013 for the treatment of ALK-positive NSCLC patients. However, resistance is noted within about one year of treatment with crizotinib....
