abstract
Monday, November 30, 2015
Sunday, November 15, 2015
Biomarkers to Guide Immunotherapy Treatment of Solid Tumors: Strategies to Promote Best Practices for Quality Care
CCO
Source: Biomarkers to Guide Immunotherapy Treatment of Solid Tumors: Strategies to Promote Best Practices for Quality Care
Module
Robert A. Anders, MD, PhD; Michael B. Atkins,
MD; Naiyer Rizvi, MD; and Janis M. Taube, MD, MSc, discuss the evolving
role of biomarkers to identify patients with cancer most likely to
benefit from immune checkpoint inhibitors.
Learning Objectives
Upon completion of this activity, participants should be able to:
- Describe the role of the immune system in pathogenesis and cancer
- Explain the mechanism of action and targeted pathways of various classes of immunotherapies
- Describe the status of emerging biomarkers being evaluated in clinical trials that may affect immunotherapy treatment decisions in the near future
- Identify patients with cancer who are likely to benefit from treatment with immunotherapy
Topics covered include:
- The Immune System in Cancer
- The Immune Response to Cancer and Opportunities for Active Immunotherapy
- Immune Checkpoint Blockade
- PD-L1 as a Potential Biomarker for Immune Checkpoint Inhibitors
- The Status of PD-L1 Biomarker Testing in the Clinic
- Other Investigational Biomarkers for Immune Checkpoint Inhibitors
Ovarian cancer and genetic counseling/testing: Who is being referred? Survey
Survey
The goal of
this survey is to find out whether or not people with ovarian cancer and
their close relatives have been offered genetic counseling and/or
genetic testing. In order to do this, we are sending out this short
online survey through online support groups for ovarian cancer. We
aim to reach as many people as possible nationwide (or even worldwide)
with either a personal history of ovarian cancer, or those who have a
relative with ovarian cancer. We hope to better understand the
experiences of people with ovarian cancer or a family history of ovarian
cancer, regardless of whether or not they have been offered
or undergone genetic testing.
If you have ever been diagnosed with ovarian cancer, or if you have
a mother, sister, or daughter who has been diagnosed with ovarian
cancer, you are eligible to participate in our survey. You can be any
gender to take our survey, but you must be 18 years old or older.
This
is a voluntary 26 question survey, and it will take about 15-20 minutes
to complete. All answers are completely anonymous with no risks to the
participants. You may exit the survey at any time. Questions marked
with an asterisk (*) are required. Please only take this survey once.
This
study is being conducted as part of a Master’s thesis requirement by a
student in the Department of Genetic Counseling at the University of
Arkansas for Medical Sciences and has received Institutional Review
Board (IRB) approval: Protocol #204292.
If you have any questions about the survey, please email us at ccook2@uams.edu
We greatly appreciate your responses!
This is a voluntary 26 question survey, and it will take about 15-20 minutes to complete. All answers are completely anonymous with no risks to the participants. You may exit the survey at any time. Questions marked with an asterisk (*) are required. Please only take this survey once.
This study is being conducted as part of a Master’s thesis requirement by a student in the Department of Genetic Counseling at the University of Arkansas for Medical Sciences and has received Institutional Review Board (IRB) approval: Protocol #204292.
If you have any questions about the survey, please email us at ccook2@uams.edu
We greatly appreciate your responses!
Saturday, November 14, 2015
Antiemetics: American Society of Clinical Oncology Focused Guideline Update
ASCO
Recommendations All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. The remaining recommendations from the 2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki.
Natural selection, inflammation may hold key to age-associated cancer risk (in mice)
Natural selection, inflammation may hold key to age-associated cancer risk: Without age-associated inflammation, older mice developed leukemia no faster than young mice
The incidence of cancer increases with age. Conventional wisdom blames this on age-dependent accumulation of cancer-causing mutations. A University of Colorado Cancer Center study published in the Journal of Clinical Investigation tells another story......
Journal Reference:
- Curtis J. Henry, Matias Casás-Selves, Jihye Kim, Vadym Zaberezhnyy, Leila Aghili, Ashley E. Daniel, Linda Jimenez, Tania Azam, Eoin N. McNamee, Eric T. Clambey, Jelena Klawitter, Natalie J. Serkova, Aik Choon Tan, Charles A. Dinarello, James DeGregori. Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors. Journal of Clinical Investigation, 2015; DOI: 10.1172/JCI83024
NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines
abstract
We
have earlier demonstrated that breast cancer and small-cell lung cancer
express functional NMDA receptors that can be targeted to promote cancer
cell death. Human ovarian cancer tissues and human ovarian cancer cell
lines (SKOV3, A2008, and A2780) have now been shown to also express
NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen
ovarian cancers in two arrays were screened by immunohistochemistry
using polyclonal antibodies that recognize an extracellular moiety on
GluN1 and on GluN2B. These specimens comprised malignant tissue with
pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid
adenocarcinoma, and clear-cell carcinoma. Additionally, archival
tissues defined as ovarian adenocarcinoma from ten patients treated at
this institute were also evaluated. All of the cancerous tissues
demonstrated positive staining patterns with the NMDA-receptor
antibodies, while no staining was found for tumor-adjacent normal
tissues or sections of normal ovarian tissue. Human ovarian
adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to
express GluN1 by Western blotting, but displayed different levels of
expression. Through immunocytochemistry utilizing GluN1 antibodies and
imaging using a confocal microscope, we were able to demonstrate that
GluN1 protein is expressed on the surface of these cells. In addition to
these findings, GluN2B protein was demonstrated to be expressed using
polyclonal antibodies against this protein. Treatment of all ovarian
cell lines with antibodies against GluN1 was found to result in
decreased cell viability (P<0.001), with decreases to 10%-25%
that of untreated cells. Treatment of control HEK293 cells with various
dilutions of GluN1 antibodies had no effect on cell viability. The GluN1
antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist
ifenprodil, like antibodies, dramatically decreased the viability of
A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor
xenografts with ifenprodil (2.5 mg/kg body weight/day) significantly
reduced tumor growth in nu/nu mice. Our findings suggest that both GluN1
and GluN2B proteins as membrane components could be readily available
targets for the treatment of most ovarian cancers.
Pharmacodynamic markers and clinical results from the phase 2 study of the SMAC mimetic birinapant in women with relapsed platinum-resistant or -refractory epithelial ovarian cancer
abstract
BACKGROUND:
Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. It was hypothesized that blocking IAPs with birinapant would increase tumor cell death and result in objective responses for women with platinum-refractory and -resistant ovarian cancer.METHODS:
In this phase 2, Cancer Therapy Evaluation Program-sponsored study, patients received birinapant at 47 mg/m2 on days 1, 8, and 15 of 28-day cycles. Pharmacokinetics were obtained during cycle 1. Plasma, peripheral blood mononuclear cells (PBMCs), and percutaneous tumor biopsy samples were collected before cycle 1 and after 6 weeks. The primary endpoint was an objective response or progression-free survival lasting greater than 6 months in a mini-max design.RESULTS:
Eleven patients received birinapant; after this, accrual was terminated for lack of a clinical benefit. Birinapant was well tolerated, with predominantly grade 2 adverse events and 1 case of grade 3 lymphopenia. Pretreatment biopsy samples and PBMCs were collected; paired posttreatment biopsy samples and PBMCs were collected from 7 and 10 patients, respectively.Friday, November 13, 2015
Ovarian Cancer National Conference – July 8-11, 2016
OCNA
Join us for the 19th Ovarian Cancer National Conference
presented by:
Register Today »
July 8-11, 2016
Washington, DC
Register to attend
Register and join us at the Ovarian Cancer National Conference.Register Today »
Antioxidants Accelerate the Growth and Invasiveness of Tumors in Mice - NCI
National Cancer Institute
.....Based on the available evidence, Dr. Bergö said he was extremely concerned with the aggressive marketing of antioxidants to cancer patients. The data strongly suggest that using antioxidants “could be really dangerous in lung cancer and melanoma, and possibly other cancers,” he said. “And because there’s no strong evidence that antioxidants are beneficial, cancer patients should be encouraged to avoid supplements after they have a diagnosis.”
Cancer surgical care, outcomes vary widely across Canada
Health - CBC News
Five types of cancer were included in the report — lung, ovarian, pancreatic, liver and esophageal — for which the surgical route is often considered complex and high risk, although still the best chance for a cure or the management of the disease if it's caught in the earlier stages.
Report:
Approaches To High-Risk, Resource Intensive Cancer Surgical Care In Canada
Thursday, November 12, 2015
Commentary: PD-L1 Expression as a Predictive Biomarker: Is Absence of Proof the Same as Proof of Absence?
JAMA Network - full text
.... Identifying the subset of patients who are most likely to respond to anti–PD-L1 therapy is the first step toward individualized therapy. As a biomarker, however, PD-L1 immunohistochemistry offers poor sensitivity and reproducibility, and as a result, these patients may be unfairly excluded from clinical trials. To offer this potentially life-saving personalized immune-based therapy to as many patients as possible, we need to develop a multifaceted predictive biomarker system that integrates checkpoint inhibitors such as PD-L1, tumor mutations, and inflammatory cells.
PD-L1 Testing in Cancer: Challenges in Companion Diagnostic Development
JAMA Network - full text
CONCLUSIONS
The
codevelopment of effective, safe anti–PD-1/PD-L1 agents with companion
diagnostic assays faces significant challenges that could impede
advancement of this therapeutic class if not properly addressed.
Harmonization of current PD-L1 assays would standardize testing, provide
guidelines for optimal PD-L1 evaluation, and may potentially circumvent
this looming problem.
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