Target Treatment Zeroes in on Cancer, Like Smart Bomb

choi

Ron Winslow, Gene Breakthroughs Spark a Revoluton in Cancer Treatment. Wall Street Journal, Aug 13, 2013 (front page).
http://online.wsj.com/article/SB ... 57473861805376.html

Note:
(a) The English surname Winslow is from a place of the same name in Buckinghamshire made up of Old English wine (meaning ‘friend’) + hlaw ‘hill’, ‘mound’, ‘barrow.’
(b) "Ms [Kellie] Carey, who worked for a business selling private jets"

"Kellie Carey Private Jets LLP
(212) 223-3231
117 E 57th St, New York, NY 10022"
Yellow Pages (New York, New York), undated.
http://www.yellowpages.com/new-y ... te-jets-llp-4040599

(c) In the past year there has been numerous news reports from reputable media outlets (New York Times is another) touting the miracle of modern medicine in treaing cancers. Specifically, DNA sequencing, in some cases the entire DNA (the jargon is "genome") of the cancer patients. So often, many mutations in a single cancer are found, and nobody knows how to interpret them (mutations). Are they--or is any of them-the cause or consequence of cancer?  I hate to be the Grinch who stole Christmas, but the hype is castle in the air.

(i) Xalkori. Pfizer, undated.
labeling.pfizer.com/showlabeling.aspx?id=676‎  

Quote:

"There are no data available demonstrating improvement in patient reported outcomes or survival with XALKORI.

"Detection of ALK-positive NSCLC [non-small-cell lung cancer] using an FDA- approved test, indicated for this use, is necessary for selection of patients for treatment with XALKORI approved test, indicated for this use, is necessary for selection of patients for treatment with XALKORI.

(ii) The first paper linking DNA mutations with NSCLC was published in 2004.

Paez JG et al, EGFR Mutations in Lung Cancer; Correlation with clinical response to Gefitinib therapy. Science, 304: 1497-1500 (2004)


identified three point mutation: G719S, L858R (CTG→ CGG), and 15-nucleotide deletions eliminating EGFR codons 746 to 750, starting at nucleotide 2235 or 2236 (Del-1).

The report could only show one of the these mutations were found in cancerous tissue but not normal tissue of a patient.

(iii) Then three years later:

Soda M et al, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448: 561–566 (2007)

reported a gene fusion of EML4 and ALK in cancerous tissue but not in normal tissue of patients. The two genes, normally located in different chromosomes, are each broken in half and fuse with remanent of the other gene, in a reciprocal manner. The evidence of import, in authors' view, is when the mutation was introduced into a mouse cell line (of fibroblast, not of lung tissue), the cells died if an ALK inhibitor was added.  

Cf
EML4-ALK positive lung cancer
http://en.wikipedia.org/wiki/EML4-ALK_positive_lung_cancer

(iv) Both EGFR (epidermal growth factor receptor) and ALK are tyrosine kinases (which adds a phosphate to certain tyrosine(s) of a substrate protein). And ALK usually appears in certain cells of nervous tissue only--so its expression in lung cancer might be meaningful. Or not (in my view).
(v) In any event, nobody has offered proof that these mutations CAUSE lung cancer, or that inhibitors of the two tyrosine kinases statistically prolong patients' life and/or improve quality of life. A few anecdotes do not prove anything.