Tuesday, September 13, 2016

A Quick List of Precision Oncology Skeptics

Just a few days after a major report of ten oncology initiatives was produced by the Cancer Moonshot advisors (here), Derek Lowe blogged at SCIENCE about a pair of skeptical articles on precision oncology, written this year by Vinay Prasad in Nature and Lancet.   A quick set of links for the curious.  Further below, a short roster of some other precision medicine skeptic articles.

September 12, 2016
"Precision Oncology Isn't Quite There Yet."
Science Translational Medicine [Blog; links therein].   by Derek Lowe.  Here.




[More after break].



A blog on Prasad's article at Genomeweb:

September 12, 2016
"Maybe Someday, Maybe Not."
Genomeweb [Blog; links therein].  The Scan.  Here.

Prasad's two 2016 articles:

September 8, 2016
PRASAD Article #2:  "Perspective: The Precision Oncology Illusion."
Nature.  By Vinay Prasad.  Here.

February, 2016
PRASAD Article #1:  "Precision Oncology: Origins, Optimism, and Potential."
Lancet Oncology.  By Vinay Prasad et al.   Here.
[Article is more skeptical than its title.]
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On similar themes see also:

October 2016
"Will Precision Medicine Improve Population Health?"
JAMA 316:1357.  By Muin Khoury & Sandro Galea.  Here.
Arguments pro and con; more con's than pro's presented.

"What Happens When  Underperforming Big Ideas in Research Become Entrenched?"
NEJM 316:1355.  By Michael Joyner et al.  Here.
"The complex and adaptive nature of most tumors thwarts the optimistic projections for molecularly targeted therapy for cancer." 

"Amid Challenges of Studying Precision Oncology, Experts Continue Trying to Measure Impact."
Genomeweb.  By Turna Ray.  Here.

September 2016
"Limits to Personalized Cancer Medicine."
NEJM 375:1289.   By IF Tannock & JA Hickman.  Here.
    Letters, January 5, 2017, here.

August 2016
"Uncertainty in the Era of Precision Medicine."
NEJM 375:711.  By DJ Hunter.   Here.
[On the MINDACT/TRANSBIG breast cancer trial]

August 2016
"Role of Genomic Profiling in Breast Cancer: Two Faces of Janus."
Transl Oncogenomics 8(S1):1.   By Y Eralp.  Here.

June 2016
"Confronting the Challenges of Precision Oncology."
Science Translational Medicine.  By Himisha Beltran.  Here.

May 2016
"Concensus on Precision Medicine for Metastatic Cancers."
Annals Oncology 27:1443.  By C Swanton et al.  Here.
   Not strictly "skeptical" but rigorously conservative.  Cited in Tannock & Hickman (2016).

April 2016
"Genetics of drug efficacy: Opportunities and Challenges."
Nat Rev Genet 17:197.  By Nelson MR et al.  Here.
"Only a small proportion of drugs have germline genetic predictors with clinically meaningful effects."

December 2015
"Characteristics of Exceptional or Super Responders to Cancer Drugs."
Mayo Clin Proc.   by Vinay Prasad and A Vandross.  Here.
"There is incompleteness in the reporting of relevant data that may help clarify whether such responses are secondary to treatment or reflect underlying biology."

October 2015
"Brave-ish New World—What’s Needed to Make Precision Oncology a Practical Reality."
JAMA Oncol.  By Laura MacConaill et al.   Here.

September 2015
"Seven Questions for Personalized Medicine."
JAMA 314:999.  By Michael Joyner & Nigel Paneth.  Here.
(For rejoinders to Joyner, here.)

As an entry to earlier citations, see a blog on "hope and hype" in precision medicine, from August 2015 -  here.  See also Joyner's anti-Moonshot op ed in  the January 2015 NYT here, and blog follow ups here, here.

For a parallel idea that comes from outside the mainstream "precision medicine" space, in clinical genetics there is a growing literature on defining "missing heritability" - the gap between genetics and phenotype.  There are clearly crosswalks between this idea in the field of biology/clinical genetics and the concern that genomics alone will only get us so-far in curing cancers.   For an open access entry point, see Blanco-Gomez, Bioessays 2016, here; see also a search of Pubmed for the phrase "missing heritability" in article titles (79 hits as of 10/1/2016).  However, be aware that even the skeptical idea of "missing heritability" has its own skeptics (!), here.
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For an example of a recent, highly positive news article in the San Diego Union, see here.  For a 16p state of the art precision medicine review article, in Nature Reviews Genetics by Stanford's Euan Ashley, see here (linked from the San Diego Union news article; Nature article 9/2016).