Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial.

Purpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).

Patients And Methods: Patients with AST received SBRT (30-50 Gy in 3-5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.

A Validated T Cell Radiomics Score Is Associated With Clinical Outcomes Following Multisite SBRT and Pembrolizumab.

Purpose: Combining immune checkpoint blockade (ICB) with stereotactic body radiation therapy (SBRT) may improve the local response to radiation and the systemic response to immunotherapy. However, no prognostic markers exist to identify patients likely to benefit from combined therapy. The degree of T cell-mediated immunity, which can be quantified with radiomics using computed tomography (CT) imaging, is predictive of immunotherapy response.

Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines.

Purpose: Glioblastoma multiforme (GBM) is an aggressive primary brain tumor that is radio-resistant and recurs despite aggressive surgery, chemo, and radiotherapy. Autotaxin (ATX) is over expressed in various cancers including GBM and is implicated in tumor progression, invasion, and angiogenesis. Using the ATX specific inhibitor, PF-8380, we studied ATX as a potential target to enhance radiosensitivity in GBM.

Cytosolic phospholipaseA2 inhibition with PLA-695 radiosensitizes tumors in lung cancer animal models.

Lung cancer remains the leading cause of cancer deaths in the United States and the rest of the world. The advent of molecularly directed therapies holds promise for improvement in therapeutic efficacy. Cytosolic phospholipase A2 (cPLA2) is associated with tumor progression and radioresistance in mouse tumor models.

DCE-MRI analysis methods for predicting the response of breast cancer to neoadjuvant chemotherapy: pilot study findings.

Purpose: The purpose of this pilot study is to determine (1) if early changes in both semiquantitative and quantitative DCE-MRI parameters, observed after the first cycle of neoadjuvant chemotherapy in breast cancer patients, show significant difference between responders and nonresponders and (2) if these parameters can be used as a prognostic indicator of the eventual response.

Methods: Twenty-eight patients were examined using DCE-MRI pre-, post-one cycle, and just prior to surgery. The semiquantitative parameters included longest dimension, tumor volume, initial area under the curve, and signal enhancement ratio related parameters, while quantitative parameters included K(trans), v(e), k(ep), v(p), and τ(i) estimated using the standard Tofts-Kety, extended Tofts-Kety, and fast exchange regime models.

Machine learning for predicting the response of breast cancer to neoadjuvant chemotherapy.

Objective: To employ machine learning methods to predict the eventual therapeutic response of breast cancer patients after a single cycle of neoadjuvant chemotherapy (NAC).

Materials And Methods: Quantitative dynamic contrast-enhanced MRI and diffusion-weighted MRI data were acquired on 28 patients before and after one cycle of NAC. A total of 118 semiquantitative and quantitative parameters were derived from these data and combined with 11 clinical variables.

High-throughput identification of putative receptors for cancer-binding peptides using biopanning and microarray analysis.

Phage-display peptide biopanning has been successfully used to identify cancer-targeting peptides in multiple models. For cancer-binding peptides, identification of the peptide receptor is necessary to demonstrate the mechanism of action and to further optimize specificity and target binding. The process of receptor identification can be slow and some peptides may turn out to bind ubiquitous proteins not suitable for further drug development.

GSK-3β: A Bifunctional Role in Cell Death Pathways.

Although glycogen synthase kinase-3 beta (GSK-3β) was originally named for its ability to phosphorylate glycogen synthase and regulate glucose metabolism, this multifunctional kinase is presently known to be a key regulator of a wide range of cellular functions. GSK-3β is involved in modulating a variety of functions including cell signaling, growth metabolism, and various transcription factors that determine the survival or death of the organism. Secondary to the role of GSK-3β in various diseases including Alzheimer's disease, inflammation, diabetes, and cancer, small molecule inhibitors of GSK-3β are gaining significant attention.

Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning.

The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery.