OBR Daily Commentary

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Scientists Identify Unique Genomic Features in Testicular Cancer

(Dana-Farber) Nov 30, 2016 - Researchers led by scientists at Dana-Farber Cancer Institute say they have identified unique genomic changes that may be integral to testicular cancer development and explain why the great majority are highly curable with chemotherapy – unlike most solid tumors.

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Debu Tripathy, MD (Posted: December 04, 2016)

quotesThese findings are an example of the power of genomic sequencing and bioinformatic analysis - with a small number of cases of testicular cancer, investigators at the Dana-Farber Cancer Institute were able to make two important, but still preliminary observations. One is that reciprocal loss of heterozygosity - that is, the simultaneous loss and gain of different pieces of the chromosome (presumably genes, or regulator of gene expression) can affect resistance to standard chemotherapy. The other (not so novel) is that p53, a well-known "guardian of the genome", is important for treatment responsiveness - many tumors that lose this gene function are more treatment resistant, and the rare hereditary loss of these gene spells risk for multiple cancers at very young ages. Of note, elephants were recently found to have multiple copies of p53 in their genome - perhaps protecting them to a greater extent from cancer). This is the first step in a new trajectory - using this information to sort out what genes and pathways offer new targets. While we keep hearing about this general theme in publications and grants, the devil is in the details - it is not only about inhibiting one gene or protein, but modulating a multi-dimensional network, and one that probably varies significantly among individual tumors.quotes

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Chinese Scientists Use Gene-Editing Techniques in Humans for First Time

(CNN) Nov 15, 2016 - Chinese scientists have become the first in the world to use the revolutionary CRISPR-Cas9 gene-editing technique in humans.

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Debu Tripathy (Posted: November 17, 2016)

quotesThe power tool of gene editing using the CRISPR (Clustered regularly interspaced short palindromic repeats) system has been used in the lab to generate cells with sculpted genes at a reasonably high fidelity. The ability to study a gene's functions and consequences of loss or gain of function or to even screen the effect of many genes has been greatly facilitated. The controversial use in humans is really an extension of ex-vivo manipulations that have already been in place with engineered cells - most notably chimeric receptor (CAR) T cells, which have yielded impressive results in clinical trials as immunotherapy in hematological malignancies and being reviewed by the FDA for approval. This report from China represents the first application of CRISPR in a human to delete immune checkpoint function and could yield greater and longer term immunotherapy, but also could leave the patient with a permanent auto immune syndrome, or worse, some new and unpredicted phenotype of the immune cell, including malignant transformation. Of course, we will not advance the medical field without taking risks - so the question is not whether to move forward or not, it is a matter of when. Have we carefully maximized the safety, monitoring plan and informed consent process in passing through this new boundary?quotes

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Protection From Trastuzumab Cardiotoxicity in Breast Cancer

(Medscape Medical News) June 23, 2016 - A new attempt at cardioprotection has failed. The first trial testing the angiotensin II-receptor blocker candesartan (Atacand, AstraZeneca) found that it did not prevent or help neutralize the cardiotoxic effects of trastuzumab (Herceptin, Genentech) in patients with early breast cancer.

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Debu Tripathy, MD (Posted: June 26, 2016)

quotesThis sobering report shows that angiotensin blockade, long postulated to protect the heart from trastuzumab-related cardiomyopathy did not do so in a placebo-controlled randomized trial. The angiotensin II antagonist candesartan did not lower the primary endpoint - rate of ejection fraction drop of more than 15% or a decrease below the absolute value 45% in a Dutch study of 206 patients receiving adjuvant trastuzumab and anthracycline/taxane-based chemotherapy. In fact, there were more events in the candesartan group, but not statistically significant. However, in a smaller study present at San Antonio in 2015 (MANTICORE Trial), both angiotensin converting enzyme inhibitor perindopril and beta blocker bisoprolol lowered the number of patients who had to discontinue trastuzumab due to EF drops, but did not significantly change EF drop itself. Further studies targeting more vulnerable patients (either genetic predisposition, which remains a subject of study, or those who are older or with low-normal EFs) are needed. These should probably include the intervention during all of the chemotherapy phase including anthracycline (which was not the case in either of the studies described). We have to remember that late cardiac events from trastuzumab exposure are still possible as we have just passed the 10th anniversary of its approval in the adjuvant setting. In addition, 5-20% may not complete therapy due to transient subclinical cardiac dysfunction, and of the rarer patients who develop clinical cardiomyopathy, up to a quarter do not recover. quotes

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Meet the Editorial Board

Community Oncology
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Dean Gesme, MD

FACP FACPE FASCO President, Minnesota Oncology...

Breast Cancer
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Debu Tripathy, MD

Professor and Chair, Department of Breast Medical Oncol...

Lung Cancer
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H. Jack West, MD

Medical Director, Thoracic Oncology Program, Swedish Ca...

Gastrointestinal Cancers
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Howard S. Hochster, MD

Associate Cancer Center Director, Yale Cancer Center P...

Radiation Oncology
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Howard Sandler, MD, MS, FASTRO

Ronald H. Bloom Chair in Cancer Therapeutics
Pr...

Community Oncology
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Jeff Patton, M.D.

CEO Tennessee Oncology...

Precision Medicine Section Editor
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Jennifer Levin Carter, MD, MPH

Chief Medical Officer and Founder, N-of-One...

Financial Sector
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Michael G. King Jr.

Managing Director and Senior Biotechnology Analyst...

Gastrointestinal Cancers
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Richard Goldberg, MD

Director WVU Cancer Institute Director of Cancer Signa...

Editor-In-Chief
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Robert A. Figlin, MD., FACP

Professor and Director, Division of Hematology Oncology...

Health Policy
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Ted Okon

Executive Director Community Oncology Alliance...

Community Oncology
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Thomas Marsland, MD

Vice President Integrated Community Oncology Network ...

Community Oncology
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William Harwin MD

Florida Cancer Specialists President and Managing Part...

Health Policy
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William McGivney, PhD

National Health Policy Expert...

Payer
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Winston Wong, PharmD

President, W-Squared Group...