Cancer: NYT Magazine (I)

choi

The past Sunday (May 15, 2016), the cover story of New York Times Magazine is

The New Anatomy of Cancer; In the past decade, researchers have revolutionized our understanding of medicine's most vexing foe -- and our prospects for treating it. A Special Report.

(I think it is a hype. There are three articles about cancers. The first is too much and I see no science.)

(1) Siddhartha Mukherjee (MD, for medical doctor), Doctor Without Border; For an oncologist in an era of rapidly proliferating, precisely targeted treatments, every case is an improvisation.
("Tarceva, a targeted therapy for lung cancer, works powerfully if the patient's cancer cells happen to [pssess a particular mutant form of a gene; for lung-cancer patients lacking that mutatio, it may be no different from taking a placebo")

Note: This oncologist of Columbia University is wrong. The following information is from the pharmaceutical itself Genetech, which is a subsidiary of Roche Group.
(a) Tarceva Mechanism of Action
http://www.tarceva.com/hcp/nsclc/moa

"Wild-type EGFR[:] In EGFR wild-type disease, tumors are reliant on the EGFR signaling pathway.

"Mutation-positive EGFR[:] In EGFR mutation-positive disease, NSCLC tumors are highly dependent on the EGFR signaling pathway.

"Tumor Proliferation and Survival[:] Tarceva inhibits EGFR and its signaling, thereby impeding tumor proliferation and survival in both EGFR wild-type and EGFR mutation-positive (exon 19 deletions and exon 21 [L585R] substitution mutations) NSCLC"  (the second set of brackets in original)

footnote 1 indicates the information is from "Tarceva [package insert]. Northbrook, IL: OSI Pharmaceuticals, LLC, an affiliate of Astellas Pharma US, Inc.; 2015." (brackets in original)
(b) Tarceva® (erlotinib) tablets in Non-Small Cell Lung Cancer. Genetech, undated.

"The EGFR Pathway and Tarceva (Proposed Mechanism of Action)
* * *
"2. Tarceva attaches to EGFR, which are responsible for bringing signals into the cell that tell it to grow and divide. These signals occur when certain proteins attach to EGFR.

"3. Tarceva works inside the cell by stopping EGFR signaling, even when mutations [exon 19 deletions and exon 21 [L585R] substitution mutations)] that keep EGFR locked in an active state are not present.

"4. By blocking EGFR activity, Tarceva may help slow or stop the growth of tumors.

(c)
(i) EGFR = epidermal growth factor receptors

(When epidermal growth factor (EGF; from outside the cell) binds to epidermal growth factor receptors (EGFR, which spans across the cellular membrane) on the surface, there is phosphorylation (addition of phosphate) on the part of EGFR inside the cell, which then transmits the signal inward like a cascade, involving a series of specific proteins step by step.)
(ii) Non-Small Cell Lung Cancer (NSCLC) accounts for 90% of lung cancers. Small Cell Lung Cancer makes up the rest.
(iii) The "wild-type" EGFR means found on healthy persons, lack of the mutations (on exons 19 and 21). There is no need for you to know what an "exon" is.  Indeed, how the mutations "keep EGFR locked in an active state" -- (b)(3) -- is unclear.

(d) Tarceva acts on both "wild-type" and "mutation-positive" EGFR.
(e) NSCLC patients have either "wild-type" or "mutation-positive" EGFR -- but not both.
(f) Normal cells of a NSCLC patients have wild-type EGFR -- but never mutation-positive EGFR.
(g) So when the patient takes in Tarceva, the drug hurts both normal and cancer cells, likely to a larger extent for the latter.