Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis

Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs

MLN8054, a small molecule inhibitor of aurora kinase a, sensitizes androgen-resistant prostate cancer to radiation.

To determine whether MLN8054, an Aurora kinase A (Aurora-A) inhibitor causes radiosensitization in androgen-insensitive prostate cancer cells in vitro and in vivo.Journal ArticleResearch Support, U.S. Gov't, Non-P.H.S.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Enhanced radiosensitivity of androgen-resistant prostate cancer: AZD1152-mediated aurora kinase B inhibition

info:eu-repo/semantics/publishe

Combining registration and active shape models for the automatic segmentation of the lymph node regions in head and neck CT images

Purpose: Intensity-modulated radiation therapy (IMRT) is the state of the art technique for head and neck cancer treatment. It requires precise delineation of the target to be treated and structures to be spared, which is currently done manually. The process is a time-consuming task of which the delineation of lymph node regions is often the longest step. Atlas-based delineation has been proposed as an alternative, but, in the authors’ experience, this approach is not accurate enough for routine clinical use. Here, the authors improve atlas-based segmentation results obtained for level II–IV lymph node regions using an active shape model (ASM) approach

PREVLAR: Phase 2a randomized trial to assess the safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving head and neck chemoradiotherapy

INTRODUCTION: No FDA-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule which impacts key pathways involved in OM pathogenesis. This Phase 2a, multi-institutional trial was designed to assess the safety and feasibility of three schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. METHODS: This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into four cohorts. In arms 1-3, RRx-001 was co-infused with patients\u27 blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using WHO criteria. Safety outcomes were assessed using NCI-CTCv4 benchmarks. Long-term tumor response was defined by RECIST v1.1 criteria. RESULTS: Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all three active arms, the study drug was infused fully per protocol in 86% of patients. All three RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; Arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least one day of SOM . There were no locoregional failures in any patient. CONCLUSIONS: Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy

A Randomized Feasibility Trial to Evaluate Use of the Jaw Dynasplint to Prevent Trismus in Patients With Head and Neck Cancer Receiving Primary or Adjuvant Radiation-Based Therapy

Objective: This study was designed to assess the feasibility of using the Jaw Dynasplint System as an adjunct to conventional stretching exercises as a preventative measure against trismus in patients undergoing radiotherapy. Methods: Study participants (n = 40) were randomized using a permuted block design to conventional stretching or stretching plus use of the Jaw Dynasplint 3 times per day for 30 minutes. Patients were instructed to record maximum interincisal opening each day as well as logging use of the Jaw Dynasplint. Results: At 6 months after initiation of the preventative regimen, 50% of patients in the Dynasplint arm and 75% in the conventional stretching arm remained on their assigned therapy. Trismus was diagnosed in 2 patients in the control arm and in 4 patients in the Dynasplint arm. Only 25% (95% confidence interval = 11.1, 46.9) of patients in the Dynasplint arm used the device as prescribed. Conclusions: The addition of the Jaw Dynasplint decreased compliance compared with conventional stretching. It is unlikely that the prescribed regimen will prove efficacious as a preventative measure due to low compliance