Introduction: moving beyond chemotherapy

Epithelial ovarian cancer and related cancers arising in extrauterine Mullerian epithelium are generally chemosensitive—particularly to the platinum drugs, cisplatin and carboplatin, that form the backbone of first-line treatments upon diagnosis even at early stages. Doublets of platinums with paclitaxel have represented the standard-of-care since the late 1990s, with further notable advances taking place by intraperitoneal administration (in Gynecologic Oncology Group studies) after optimal surgical cytoreduction is achieved, and by divided doses of paclitaxel (in a Japanese GOG study). Adding another agent to improve on these results has otherwise proven to be quite challenging. Nevertheless, continued forays into introducing ‘targeted therapies’ are beginning to bear fruit, and form part of this Translational Cancer Research ( TCR ) supplement. The purpose of this supplement is to provide a summary of the advances in tumor biology and a glimpse into where targeted therapeutics are moving, and their successes to date

Integrating targeted drugs with taxanes and platinums: opportunities and challenges

In ovarian cancer, multiple attempts to adjust the standard taxane/platinum doublet by adding cytotoxic therapy or varying scheduling, dosage, and delivery have been met with limited success. Alternative methods to improve the grim prognosis of ovarian cancer, including molecular therapies, are currently under investigation. Efforts have been made to study tyrosine kinase inhibitors (including imatinib and pazopanib), Src kinase inhibitors and histone deacetylase inhibitors (HDACi) in combination with taxanes/platinums in order to improve efficacy. Unfortunately, while many pre-clinical and early phase clinical trials argue that the utilization of these molecular targets may enhance survival, only modest benefit has been seen in larger clinical trials. Other agents that have been evaluated include proteasome inhibitors, folate receptor antagonists, MEK inhibitors and opiate antagonists. In this review, we discuss the mechanisms of these targeted therapies and highlight the current and ongoing clinical trials that utilize these targeted agents in combination with taxanes and platinums in advanced ovarian cancer

Shields Up For Software

This Article contends that the National Cybersecurity Strategy\u27s software liability regime should incorporate two safe harbors. The first would shield software creators and vendors from liability for decisions related to design, implementation, and maintenance, as long as those choices follow enumerated best practices. The second—the “inverse safe harbor”—would have the opposite effect: coders and distributors who engaged in defined worst practices would automatically become liable. This Article explains the design, components, and justifications for these twin safe harbors. The software safe harbors are key parts of the overall design of the new liability regime and work in tandem with the standard of care proposed in the National Cybersecurity Strategy. The safe harbors’ role is to provide certainty to regulated entities; to reduce the administrative costs of the new regime; and to create incentives for adopting best practices or avoiding worst ones

EGFR and HER2: is there a role in ovarian cancer?

Advanced ovarian cancer carries a grim prognosis and development of targeted therapies to improve outcomes has become an active area of research in this disease. The epidermal growth factor receptor (EGFR) and HER2/neu have shown to be overexpressed in ovarian cancer and there have been several clinical trials evaluating anti-EGFR and HER2 therapies in ovarian cancer. Unfortunately, the drugs have shown minimal efficacy and more recent work has now focused on identifying mechanisms of resistance and alternative ways of targeting these pathways. This review will discuss the currently published trials with anti-EGFR and HER2 agents in ovarian cancer and the further directions of study with these pathways

Systemic Therapy for HER2-Positive Central Nervous System Disease: Where We Are and Where Do We Go From Here?

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at an increased risk of developing brain metastases. The incidence and prevalence of central nervous system (CNS) disease are increasing due to improved survival, which can be attributed to better systemic therapies for extracranial disease. The current standard of care for brain metastases includes a combination of surgery and/or radiation. Systemic therapies are typically reserved for patients with intracranial progression following radiation, due to their limited ability to cross the blood-brain barrier. None of the available anti-HER2 agents (trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1)) are currently approved for the treatment of brain metastases. Research is underway evaluating novel anti-HER2 agents, which have demonstrated CNS activity. This article discusses the current data on using anti-HER2 therapies to treat CNS disease as well as the newer anti-HER2 agents, which may overcome the current challenges faced in treating brain metastases in the HER2-positive patient population

Updates in Neoadjuvant Therapy for Triple Negative Breast Cancer

© 2020 Elsevier Inc. Neoadjuvant therapy in breast cancer refers to systemic therapy administered prior to definitive surgery. It was originally developed for patients with locally advanced breast cancer (stage III) with the intention of downstaging unresectable tumors, and decreasing the extent of surgical intervention, including axillary lymph node dissection. For patients with inflammatory breast cancer, neoadjuvant therapy is considered a standard of care. Increasingly, the neoadjuvant setting is being utilized to accelerate drug development and approval in triple negative breast cancer, a diverse and aggressive subgroup for which no approved targeted therapies are currently available. This review discusses the use of pathologic complete response as a clinical trial endpoint, the use of imaging and biomarkers to predict response to therapy, and standard of care treatment for triple negative breast cancer. Finally, we review novel targets and drug trials in the neoadjuvant setting