Vol 2-4 Mini Review

Bridging the Data Gap in Breast Cancer Risk Assessment to Enable Widespread Clinical Implementation across the Multiethnic Landscape of the US

Erika Spaeth1*, Athena Starlard-Davenport2, Richard Allman3

1Phenogen Sciences Inc, Charlotte, NC 28269, USA

2Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA

3Genetic Technologies, Ltd, Fitzroy, VIC 3065, Australia

Breast cancer remains the second leading cause of cancer death among women and is the most commonly diagnosed cancer in women. Breast cancer risk assessment has been clinically available for nearly 30 years yet is under-utilized in practice for multiple reasons. Incorporation of polygenic risk as well as breast density measurements, promise to increase the accuracy of risk assessment. With that comes the hope that both prevention and screening become more personalized and thus more effective. Incidence rates have been static over the past 15 years and have even increased slightly in African American and Asian/Pacific Islander populations despite the robust data on breast cancer risk reduction measures that exist. Current challenges in reducing breast cancer incidence begin with robust data curation that allows for appropriate risk stratification across our multiethnic population and conclude with the implementation of prevention strategies within our fractured healthcare system.

DOI: 10.29245/2578-2967/2018/4.1137 View / Download Pdf View Full Text
Vol 2-4 Commentary

Therapeutic Approaches to Radiation-Induced Fibrosis

Edward J. Macarak, Joel Rosenbloom*

The Joan and Joel Rosenbloom Research Center for Fibrotic Diseases, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Radiation induced fibrosis (RIF) is a common morbidity in patients being treated for cancer with radiation. Off-target effects result in intense inflammatory responses which ultimately results in the generation of extracellular matrix (ECM) producing myofibroblasts which mediate a progressive fibrosis resulting in scarring and organ and tissue dysfunction. Unfortunately, currently, there are no effective therapies to block the excess accumulation of ECM. We have previously reported on the use of trametinib, a MEK inhibitor, to essentially block the formation of abdominal adhesions in a mouse model of cecal abrasion. Using this drug in the mouse model, the complete trans-differentiation of precursor cells into ECM-producing myofibroblasts was blocked. Trametinib is a potentially powerful drug to thwart organ and tissue fibrosis in RIF because it has a potential dual function in that it may block RIF as well as prevent radiation-resistance. Given the intractability of RIF, trametinib should be considered for more extensive testing.

DOI: 10.29245/2578-2967/2018/4.1144 View / Download Pdf View Full Text
Vol 2-4 Commentary

Value of Multiplatform Molecular Profiling (MMP) of Tumors in Clinical Practice

Ofer Purim1*, Aron Popovtzer2, Ron Epelbaum3

1Oncology Institute, Assuta Ashdod Academic Hospital, Ashdod, Israel

2Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah Tikva, Israel, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3Department of Oncology, Rambam Health Care Campus, Haifa, Israel

In the last 20 years, cancer treatment has witnessed a paradigm shift with the advent of modern targeted therapies. Still, at present, targeted therapies, despite being very effective, are only relevant for a minority of patients, whereas the majority of patients are still being offered cytotoxic drugs. The goal of this mini-review is to describe the clinical utility of tumor multi-panel molecular profiling (MMP) to guide treatment decisions (primarily chemotherapies but also targeted therapies) in patients with solid tumors and the evidence supporting this approach, focusing on the Caris Molecular Intelligence (CMI) MMP. The evidence suggests that MMP is a practical, implementable tool that can be used to personalize treatment (including that of chemotherapies), increasing the likelihood of response and sparing patients from unnecessary toxicity associated with ineffective therapies. MMP provides the ability to offer therapy to patients in later lines, particularly for those who have already failed multiple lines of therapy and exhausted the standard therapy options (by suggesting therapies which may be used off-label). Furthermore, the evidence indicates that MMP-guided therapy favorably impacts both progression-free survival and overall survival. As the current data consist of mainly retrospective studies, prospective trials are warranted to strengthen the evidence.

DOI: 10.29245/2578-2967/2018/4.1149 View / Download Pdf View Full Text
Vol 2-4 Mini Review

Mini Review: Immunohistochemistry Using EGFR-Mutant Specific Antibodies in Non-Small Cell Lung Carcinoma: Accuracy and Reliability

Rania Gaber1,2,3, Torsten Goldmann1,3*

1Pathology of the University of Lübeck and the Research Center Borstel, Site Borstel, Clinical and Experimental Pathology, Borstel, Germany

2Department of Pathology, Faculty of Medicine, Alexandria University, Alexaandria, Egypt

3Airway Research Center North (ARCN), Member of the German Center for Lung Research, Germany

Epidermal growth factor receptor (EGFR) is a predictive biomarker in many solid cancers including non-small cell lung carcinoma (NSCLC). Patients’ responsiveness to therapy is based on the prior determination of EGFR status. Many techniques were used to detect the potential predictive biomarker and considered as gold standards based on molecular genetic techniques as direct sequencing and polymerase chain reaction (PCR). Immunohistochemistry (IHC) using EGFR mutation-specific antibodies were generated as an alternative simple tool to identify EGFR status and its response to tyrosine kinase inhibitors (TKIs). EGFR gene copy number and wild-type EGFR are other parameters which determine the response to TKIs. The aim of this mini-review is to analyze the studies which investigated the IHC EGFR mutation-specific antibodies, in lung adenocarcinoma (ADC), to determine its accuracy and reliability as a pre-selection tool for candidate patients for TKIs therapy as well as the interplay with other EGFR biomarkers which are EGFR gene copy number and the wild-type EGFR in lung NSCLC. The later determine the response to TKIs and their detection methodology is standardized making them good candidates for comparison with the EGFR-mutation.

DOI: 10.29245/2578-2967/2018/4.1140 View / Download Pdf View Full Text
Vol 2-4 Mini Review

Management of Loco-Regional Nasopharyngeal Carcinoma-The Role of Induction Chemotherapy-A Mini-Review

Frank E Mott1*, Ruth L. Sacks2

1Thoracic and Head/Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Texas, USA

2University of Texas MD Anderson Cancer Center, Texas, USA

Standard treatment of locally advanced nasopharyngeal carcinoma is patterned after the Intergroup 0099 trial with concurrent cisplatin with radiotherapy, followed by consolidation chemotherapy. This remains the guideline recommended standard. With the wider use of intensity modulated radiotherapy and the incorporation of taxanes in the chemotherapy regimen, many oncologists are increasingly using an induction approach with chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy is not considered a standard approach despite studies showing efficacy and tolerability. In this mini-review, we summarize the data from trials and reviews of induction therapy and argue for its recognition as a viable standard option for patients with locally advanced nasopharyngeal carcinoma.

DOI: 10.29245/2578-2967/2018/4.1146 View / Download Pdf View Full Text