The Cancer Chronicles (40 page)

47.
A targeted drug called Alpharadin:
Christopher Parker et al., “Overall Survival Benefit of Radium-223 Chloride (Alpharadin) in the Treatment of Patients with Symptomatic Bone Metastases in Castration-Resistant Prostate Cancer,” 7th NCRI Cancer Conference, November 2011, Liverpool. [
http://www.ncri.org.uk/ncriconference/2011abstracts/abstracts/ClinicalShowcase1.html
] Also see Deborah A. Mulford, David A. Scheinberg, and Joseph G. Jurcic, “The Promise of Targeted Alpha-particle Therapy,”
Journal of Nuclear Medicine
46 suppl. 1 (January 2005): 199S–204S. [
http://www.ncbi.nlm.nih.gov/pubmed/15653670
]

1.
“Kisses for the Cure”:
Anne Landman, “How Breast Cancer Became Big Business,” PR Watch website, June 14, 2008. [
http://www.prwatch.org/node/7436
]

2.
Stand Up to Cancer telethon:
“The Show,” Stand Up to Cancer website. [
http://standup2cancer.org/theshow
] (There has since been a 2012 broadcast.)

3.
a workshop that evening at the Parker House:
“Translational Cancer Research
for Basic Scientists Workshop,” American Association for Cancer Research, October 17–22, 2010, Boston, MA.

4.
told the story of two cousins:
Amy Harmon, “New Drugs Stir Debate on Rules of Clinical Trials,”
New York Times,
September 18, 2010. [
http://www.nytimes.com/2010/09/19/health/research/19trial.html
] For more about the trial see Amy Harmon, “Target Cancer,” a series of six articles,
New York Times,
February 22, 2010, to January 20, 2011. [
http://topics.nytimes.com/top/news/health/series/target_cancer/index.html
]

5.
a mutation in a gene called
BRAF
:
As a result, the gene produces a distorted version of a protein that is part of a cellular growth pathway. Normally the BRAF protein is actuated only when it interacts with another protein called RAS, but the mutation frees it of this constraint. See “Vemurafenib,” New Treatments, Melanoma Foundation website. [
http://www.melanoma.org.nz/About-Melanoma/Diagnosis-and-Treatment/New-Treatments/Vemurafenib
] For a description of the cancer and the vemurafenib trials see Paul B. Chapman et al., “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation,”
New England Journal of Medicine
364, no. 26 (June 30, 2011): 2507–16. [
http://www.nejm.org/doi/full/10.1056/NEJMoa1103782
] For a later study see Jeffrey A. Sosman et al., “Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib,”
New England Journal of Medicine
366, no. 8 (2012): 707–14. [
http://www.nejm.org/doi/full/10.1056/NEJMoa1112302
]

6.
Phase III proved so definitive:
Andrew Pollack, “Two New Drugs Show Promise in Slowing Advanced Melanoma,”
New York Times,
June 6, 2011. [
http://www.nytimes.com/2011/06/06/health/research/06melanoma.html
]

7.
typically living four months longer:
The median overall survival was 13.2 vs. 9.6 months for dacarbazine. See Paul B. Chapman et al., “Updated Overall Survival (OS) Results for BRIM-3,” 2012 ASCO Annual Meeting,
Journal of Clinical Oncology
30 no. 18, suppl. (June 20, 2012): abstract 8502. [
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=97795
]

8.
sixty-six in the dacarbazine group:
“Clinical Trial Result Information,” protocol number NO25026, January 4, 2011, Roche trials database website. [
http://www.roche-trials.com/studyResultGet.action?studyResultNumber=NO25026
]

9.
half of the people … were dead:
Chapman, “Updated Overall Survival (OS) Results.”

10.
“he was running a race”:
Alexander Solzhenitsyn,
Cancer Ward,
trans. Nicholas Bethell and David Burg (New York: Farrar, Straus and Giroux, 1969), 250.

11.
through a fortuitous mutation:
Ramin Nazarian et al., “Melanomas Acquire Resistance to B-RAF(V600E) Inhibition by RTK or N-RAS Upregulation,”
Nature
468, no. 7326 (November 24, 2010): 973–77. [
http://www.nature.com/nature/journal/v468/n7326/abs/nature09626.html
]

12.
a paradoxical side effect:
Fei Su et al., “RAS Mutations in Cutaneous Squamous-cell Carcinomas in Patients Treated with BRAF Inhibitors,”
New England Journal of Medicine
366, no. 3 (January 19, 2012): 207–15. [
http://www.nejm.org/doi/full/10.1056/NEJMoa1105358
]

13.
experimenting with combinations:
In 2012,
The New England Journal of Medicine
reported encouraging results from a trial involving dabrafenib, a different BRAF inhibitor. It was combined with trametinib, which inhibits
MEK, another enzyme in the same cellular pathway. See Keith T. Flaherty et al., “Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations,”
New England Journal of Medicine
(published online September 29, 2012). [
http://www.nature.com/nature/journal/v468/n7326/abs/nature09626.html
]

14.
described the jarring effect:
Tom Curran, “Oncology as a Team Sport,” Translational Cancer Research Workshop, October 17, 2010.

15.
discovered a gene called reelin:
G. D’Arcangelo, T. Curran, et al., “A Protein Related to Extracellular Matrix Proteins Deleted in the Mouse Mutant Reeler,”
Nature
374, no. 6524 (April 20, 1995): 719–23; [
http://www.ncbi.nlm.nih.gov/pubmed/7715726
] and G. G. Miao, T. Curran, et al., “Isolation of an Allele of Reeler by Insertional Mutagenesis,”
Proceedings of the National Academy of Sciences
91, no. 23 (November 8, 1994): 11050–54. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC45164
]

16.
8 cases in 10 million:
Betsy A. Kohler et al., “Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System,” Journal of the National Cancer Institute 103, no. 9 (May 4, 2011), 1–23, table 5.

17.
5 cases per 100,000 among children:
Kohler et al., “Annual Report,” 12, table 6.

18.
the most common pediatric brain tumor:
Charles M. Rudin et al., “Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449,”
New England Journal of Medicine
361, no. 12 (September 17, 2009): 1173–78. [
http://www.nejm.org/doi/full/10.1056/NEJMoa0902903#t=abstract
]

19.
median age of diagnosis is five:
Rudin, “Treatment of Medulloblastoma.”

20.
“a clumsy, staggered walking pattern”:
“Medulloblastoma,” American Brain Tumor Association website (2006), 6. [
http://www.abta.org/understanding-brain-tumors/types-of-tumors/medulloblastoma.html
]

21.
the five-year survival rate was as high as 80 percent:
“Medulloblastoma,” 17.

22.
“I met one kid, a teenager”:
Curran, “Oncology as a Team Sport.”

23.
research from other labs:
For an overview see Ken Garber, “Hedgehog Drugs Begin to Show Results,”
Journal of the National Cancer Institute
100, no. 10 (May 21, 2008): 692–97. [
http://jnci.oxfordjournals.org/content/100/10/692.extract
]

24.
the story of the cyclopean lambs:
This is told in chapter 6 of this book.

25.
a meeting on brain genetics and development:
Genetic Basis of Brain Development and Dysfunction, March 18–23, 2000, Sagebrush Inn and Conference Center, Taos, New Mexico. [
http://www.keystonesymposia.org/index.cfm?e=Web.Meeting.Program&MeetingID=514
] The authority on hedgehog signaling was Andrew McMahon at Harvard University.

26.
Curran went on to show:
Justyna T. Romer, T. Curran, et al., “Suppression of the Shh Pathway Using a Small Molecule Inhibitor,”
Cancer Cell
6, no. 3 (September 2004): 229–40. [
http://www.sciencedirect.com/science/article/pii/S1535610804002417
]

27.
inhibited bone development:
Garber, “Hedgehog Drugs Begin to Show Results.”

28.
there were signs that the drug … was safe:
“Experimental Targeted Therapy
Shows Early Promise Against Medulloblastomas,” St. Jude Children’s Research Hospital website, June 5, 2010. [
http://multivu.prnewswire.com/mnr/stjude/44444
]

29.
approved for basal cell carcinoma:
“FDA Approval for Vismodegib,” National Cancer Institute website. [
http://www.cancer.gov/cancertopics/druginfo/fda-vismodegib
]

30.
“forward looking”:
Emmy Wang, senior manager, corporate relations, Genentech, e-mail to author on behalf of Fred de Sauvage, March 2, 2012.

31.
a body called the United States Adopted Names Council:
For a deciphering of generic drug names see “USAN Stem List,” American Medical Association website. [
http://www.ama-assn.org/resources/doc/usan/stem-list-cumulative.pdf
]

32.
described the latest findings:
José Baselga, keynote (untitled), Translational Cancer Research Workshop, Boston, October 17, 2010.

33.
“super Herceptin” or trastuzumab emtansine:
Ion Niculescu-Duvaz, “Trastuzumab Emtansine, an Antibody-drug Conjugate for the Treatment of HER2+ Metastatic Breast Cancer,”
Current Opinion in Molecular Therapeutics
12, no. 3 (June 2010): 350–60. [
http://www.ncbi.nlm.nih.gov/pubmed/20521224
]

34.
drug called pertuzumab:
Cormac Sheridan, “Pertuzumab to Bolster Roche/Genentech’s Breast Cancer Franchise?”
Nature Biotechnology
29, no. 10 (October 13, 2011): 856–58. [
http://www.nature.com/nbt/journal/v29/n10/full/nbt1011-856b.html
]

35.
pertuzumab became Perjeta:
“FDA Approval for Pertuzumab,” National Cancer Institute website, June 11, 2012. [
http://www.cancer.gov/cancertopics/druginfo/fda-pertuzumab
]

36.
patients were outraged:
Robert Weisman, “Limits on Test Drugs Add to Patients’ Ordeals,”
Boston Globe,
January 5, 2011. [
http://www.boston.com/business/healthcare/articles/2011/01/05/testing_rules_force_patients_to_wait_for_new_drugs
]

37.
the agency insisted on waiting:
Martin de Sa’Pinto and Katie Reid, “FDA Puts Brakes on Roche, ImmunoGen Cancer Drug,”
Reuters,
August 27, 2010. [
http://www.reuters.com/article/2010/08/27/roche-idUSLDE67Q03620100827
]

38.
a rally outside Boston City Hall:
The date was December 6, 2011.

39.
“reduced the risk of cancer worsening”:
Media release, June 3, 2012, Roche website. [
http://www.roche.com/media/media_releases/med-cor-2012-06-03b.htm
] Also see Lisa Hutchinson, “From ASCO—Breast Cancer: EMILIA Trial Offers Hope,”
Nature Reviews Clinical Oncology
9, no. 8 (August 1, 2012): 430. It was approved February 22, 2013, by the FDA and is sold as Kadcyla.

40.
“smoothes and tightens the skin”:
Barbara Ehrenreich, “Welcome to Cancerland,”
Harper’s Magazine,
November 2001. [
http://www.barbaraehrenreich.com/cancerland.htm
] Also see Gayle A. Sulik,
Pink Ribbon Blues: How Breast Cancer Culture Undermines Women’s Health
, (New York: Oxford University Press, 2011).

41.
how many lives that saves:
For more on the controversy over breast cancer treatment see Robert A. Aronowitz,
Unnatural History: Breast Cancer and American Society
(Cambridge: Cambridge University Press, 2007); and David Plotkin, “Good News and Bad News About Breast Cancer,”
The Atlantic,
June 1998. [
http://www.theatlantic.com/magazine/archive/1998/06/good-news-and-bad-news-about-breast-cancer/5504
]

42.
A recent epidemiological study of 600,000 women:
P. C. Gøtzsche and M. Nielsen, “Screening for Breast Cancer with Mammography,”
The Cochrane
Library
4 (2009). A summary was published on the Cochrane website April 13, 2011. [
http://summaries.cochrane.org/CD001877/screening-for-breast-cancer-with-mammography
]

43.
a disturbing number:
Timothy J. Wilt et al., “Radical Prostatectomy Versus Observation for Localized Prostate Cancer,”
New England Journal of Medicine
367, no. 3 (2012): 203–13. [
http://www.nejm.org/action/showCitFormats?doi=10.1056%2FNEJMoa1113162
] Also see G. Sandblom et al., “Randomised Prostate Cancer Screening Trial: 20 Year Follow-up,”
BMJ: British Medical Journal
342 (March 31, 2011): d1539. [
http://www.bmj.com/content/342/bmj.d1539
]

44.
About 70 percent of men in their seventies:
For a review of the autopsy studies see Richard M. Martin, “Commentary: Prostate Cancer Is Omnipresent, but Should We Screen for It?”
International Journal of Epidemiology
36, no. 2 (April 1, 2007): 278–81. [
http://ije.oxfordjournals.org/content/36/2/278.extract
]

45.
Urologists offer free tickets:
The examples are from Gary Schwitzer, “Cheerleading, Shibboleths and Uncertainty,” a presentation on April 23, 2012, Science Writing in the Age of Denial, University of Wisconsin, Madison, WI. The urinal example was provided to Schwitzer by Ivan Oransky, the executive editor of Reuters Health.

46.
one of “the best and brightest”:
Tom Junod, “Franziska Michor Is the Isaac Newton of Biology,”
Esquire,
November 20, 2007. [
http://www.esquire.com/features/michor1207
]

47.
uncovered some of the early clues:
See, for example, J. C. Fisher, “Multiple-Mutation Theory of Carcinogenesis,”
Nature
181 (March 1, 1958): 651–52 [
http://www.nature.com/nature/journal/v181/n4609/abs/181651b0.html
]; P. Armitage and R. Doll, “The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis,”
British Journal of Cancer
8 (1954): 1–12 [
http://www.nature.com/bjc/journal/v91/n12/full/6602297a.html
]; and C. O. Nordling, “A New Theory on the Cancer-inducing Mechanism,”
British Journal of Cancer
7, no. 1 (March 1953): 68–72. [
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2007872
]