Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.
Chemical self-assembly has garnered tremendous interest as a tool for generating nanometer-scale structures and devices. Organosilane self-assembled monolayers (SAMs) are of particular interest because of their ability to assemble on a wide range of substrates with varied chemical functionalities. Nanoshaving, an atomic force lithographic technique, has been demonstrated as a method to generate nanopatterns of organosilane SAMs. However, this method requires extremely high force setpoints, which rapidly dulls atomic force microscopy tips and degrades the resolution of the resulting nanopattern. In this work, we utilize Cu-ligated mercaptohexadecanoic acid (MHDA) multilayers to circumvent this limitation. Initially, a 10-undecenyltrichlorosilane (UTS) SAM is assembled onto a Si substrate, and the terminal olefin groups of the UTS SAM are oxidized to carboxyl groups. Subsequently, a Cu-ligated MHDA multilayer is assembled via the sequential deposition of Cu2+ ions and MHDA molecules. The interface between the oxidized UTS SAM and Cu-ligated MHDA multilayer serves as a natural low force breakpoint for nanoshaving. We demonstrate that the resulting nanopatterns can function as a chemical resist to fabricate metal nanostructures.
The development of methods to produce nanoscale features with tailored chemical functionalities is fundamental for applications such as nanoelectronics and sensor fabrication. The molecular-ruler process shows great utility for this purpose as it combines top-down lithography for the creation of complex architectures over large areas in conjunction with molecular self-assembly, which enables precise control over the physical and chemical properties of small local features. The molecular-ruler process, which most commonly uses mercaptoalkanoic acids and metal ions to generate metal-ligated multilayers, can be employed to produce registered nanogaps between metal features. Expansion of this methodology to include molecules with other chemical functionalities could greatly expand the overall versatility, and thus the utility, of this process. Herein, we explore the use of alkanethiol molecules as the terminating layer of metal-ligated multilayers. During this study, it was discovered that the solution deposition of alkanethiol molecules resulted in low overall surface coverage with features that varied in height. Because features with varied heights are not conducive to the production of uniform nanogaps via the molecular-ruler process, the vapor-phase deposition of alkanethiol molecules was explored. Unlike the solution-phase deposition, alkanethiol islands produced by vapor-phase deposition exhibited markedly higher surface coverages of uniform heights. To illustrate the applicability of this method, metal-ligated multilayers, both with and without an alkanethiol capping layer, were utilized to create nanogaps between Au features using the molecular-ruler process.
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