Sneha Phadke

Bio: Sneha Phadke is an academic researcher from University of Iowa Hospitals and Clinics. The author has contributed to research in topics: Breast cancer & Medicine. The author has an hindex of 4, co-authored 13 publications receiving 102 citations. Previous affiliations of Sneha Phadke include University of Iowa & Roy J. and Lucille A. Carver College of Medicine.

Pembrolizumab Therapy Triggering an Exacerbation of Preexisting Autoimmune Disease: A Report of 2 Patient Cases.

Abstract: Historically, metastatic melanoma was uniformly and rapidly lethal, and treatment options were limited. In recent years, however, checkpoint inhibitors have emerged as an accepted standard treatment for patients with advanced melanoma. In clinical trials, these agents have been largely well tolerated and have the potential to result in durable responses. Importantly though, one must recognize the unique side effect profile of these therapies, which can trigger or exacerbate underlying autoimmune disease. Whether this autoimmune activation is associated with a clinical response to therapy has been debated, and while not definitive, there is evidence in the literature of a possible association. The 2 cases presented describe this autoimmune phenomenon, along with a review of the existing literature on the relationship between response to immunotherapy and autoimmune side effects.

Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology.

Abstract: A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: (1) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and (2) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers.

Beta blockade as adjunctive breast cancer therapy: A review.

Abstract: Pre-clinical data has shown that beta adrenergic stimulation can affect the development and progression of many types of cancer. The use of beta blockers as an anti-neoplastic therapy has been studied in retrospective trials and observational trials, but no definitive conclusions about efficacy have been made. Within the realm of breast cancer, significant advances in therapy have led to improved survival outcomes, yet there is room for improvement. Beta adrenergic blockade may prove an effective adjunct to standard breast cancer therapy, with little associated toxicity. This article provides a review of the published literature on beta blockade as an adjunctive cancer therapy, with a focus on breast cancer.

Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors.

Abstract: Conventional chemotherapeutics have been developed into clinically useful agents based on their ability to preferentially kill malignant cells, generally owing to their elevated proliferation rate. Nonetheless, the clinical activity of various chemotherapies is now known to involve the stimulation of anticancer immunity either by initiating the release of immunostimulatory molecules from dying cancer cells or by mediating off-target effects on immune cell populations. Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors (ICIs) relative to their effectiveness as monotherapies. Indeed, accumulating evidence supports the clinical value of combining appropriately dosed chemotherapies with ICIs. In this Review, we discuss preclinical and clinical data on the immunostimulatory effects of conventional chemotherapeutics in the context of ICI-based immunotherapy.

Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: A systematic review

Abstract: Background Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease. Purpose To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease. Data sources MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions. Study selection Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs. Data extraction 2 reviewers independently extracted data and assessed the quality of reporting. Data synthesis 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events. Limitations The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined. Conclusion Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk-benefit ratios and patient preferences in this population. Primary funding source National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Liquid biopsy in breast cancer: A comprehensive review

Abstract: Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free RNA, tumor-educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.

Neurological toxicities associated with immune-checkpoint inhibitors.

Abstract: Purpose of reviewImmune-checkpoint inhibitors (ICIs) constitute a novel class of agents recently approved to treat a number of human malignancies. Due to their immunomodulatory mechanism of action, ICIs can generate a wide range of immune-related adverse events (irAEs) of which neurological toxiciti