Purpose In acute lymphoblastic leukemia (ALL), multidrug resistance is often mediated by ATPase Binding Cassette (ABC) proteins, which principally involve ABCB1 (multidrug resistance 1, MDR1) and ABCC1 (multidrug resistance protein 1, MRP1). However, direct comparisons between the differential effects of ABCB1 and ABCC1 have been difficult, since identical cell lines with differential expression of these transporters have not been developed. Experimental Design In this study, we developed and compared the biological profiles of Jurkat cell lines that selectively over-expressed ABCB1 and ABCC1. Vincristine (VCR) plays an important role in the treatment of T-lineage ALL (T-ALL), and is often the first drug given to newly-diagnosed patients. Because of its importance in treatment, we provided escalating, sub-lethal doses of VCR to Jurkat cells, and extended our observations to expression profiling of newly diagnosed patients with T-ALL. Results We found that VCR-resistant cells over-expressed ABCC1 nearly 30-fold. The calcein AM assay confirmed that VCR-resistant cells actively extruded VCR, and that ABCC1-mediated drug resistance conferred a different spectrum of multidrug resistance than other T-ALL induction agents. siRNA experiments that blocked ABCC1 export confirmed that VCR resistance could be reversed in vitro. Analyses of T-lymphoblasts obtained from 92 newly diagnosed T-ALL patients treated on Children's Oncology Group Phase III studies 8704/9404 showed that induction failure could be explained in all but one case by the over-expression of ABCB1 or ABCC1. Conclusions Taken together, these results suggest that over-expression of ABC transporters plays a contributing role in mediating treatment failure in T-ALL, and underscore the need to employ alternate treatment approaches in patients for whom induction failed or for those with relapsed disease.

Although breast and ovarian cancer have notable distinctions, there may exist parallel pathways that can be exploited for therapeutic gain. For example, the therapeutic arena in breast cancer has benefited greatly from available endocrine therapies as well as novel drugs designed to target the HER2 receptor, including trastuzumab, lapatinib, T-DM1 and pertuzumab. CLEOPATRA, a Phase III randomized clinical trial studying pertuzumab in women with HER2-amplified metastatic breast cancer, was practice-changing in 2014. Its counterpart, the Phase III randomized PENELOPE trial, was activated following promising Phase II data and studied pertuzumab in an enriched ovarian cancer patient population with low HER3 mRNA. This review will trace the development of anti-HER2 therapies in breast and ovarian cancer.

Purpose of review Amidst the worldwide coronavirus disease 2019 pandemic, a new medical landscape revolving around telemedicine has arisen. The purpose of this review is to describe and analyze current urogynecologic guidelines for optimizing usage of telemedicine when treating women with pelvic floor disorders. Recent findings Women managed by urogynecologists are on average older, and hence more likely to have comorbidities that make them susceptible to developing coronavirus disease 2019 with severe symptoms. Telemedicine is key in minimizing exposure without sacrificing treatments and quality of life. Recent studies published prior to the pandemic helped set the stage for successful components of virtual care. Nonsurgical options are crucial to beginning a treatment plan while elective surgeries are still restricted in many hospitals. Medication management and innovative technology, such as smart telephone applications, play a prominent role. The comprehensive literature review discussed here describes the degree of evidence supporting each management option, while also noting the limitations of telemedicine. Summary Telemedicine has opened a new door for the field of urogynecology allowing for continued safe, evidence-based care. The pandemic culture has tipped the balance away from surgery and toward nonsurgical treatments while attempting not to sacrifice outcomes or quality of care.

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This article will review these four notable monoclonal antibodies, their role in clinical oncology, and the drug patents that are nearing expiration. There are currently only two biosimilars approved in the United States: the trastuzumab biosimilar trastuzumab-dkst (Ogivri) and the bevacizumab biosimilar bevacizumab-awwb (Mvasi). In Europe, SB3, a trastuzumab biosimilar, is approved for use as well as two rituzimab biosimilars, truxima and rixathon.

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