chickens, Rous sarcoma virus, 27, 29
Christchurch chromosome, 22
chromosome 9
abl gene on, 83
abnormal, 38
Philadelphia chromosome translocation and, 83, 84
chromosome 15, 82
chromosome 21, 82
chromosome 22, abnormal. See Philadelphia chromosome
chromosome banding techniques, 37, 58, 88
chromosomes
appearance of, 33
banding techniques, 37, 58, 88
deletions, 22, 38
Giemsa staining, 33
number of human chromosomes, 35
translocation, 39, 81, 84
chronic lymphocytic leukemia (CLL), 191
chronic myeloid leukemia (CML)
abnormal chromosome 9, 38, 83, 84
about, 4
ara-C, 193, 205
Bcr/Abl tyrosine kinase and, 86, 89, 106, 118
“blast crisis,” xiii, 5, 37, 86, 176, 178, 196, 198, 204, 216, 218, 226, 249
complete cytogenetic remission, 197
cost of treatment, 259, 265
dasatinib for, 257, 258
early treatment methods, 13
genetic mutation in, 15, 17, 83, 252, 260, 267
incidence, 114, 230
interferon for, 105, 189, 191, 205, 219, 243
long-term management of healthy patients, 260
nilotinib for, 258
non-responders, 260
number of people living with the disease, 259
patients with T315 mutation, 260
ponatinib for, 260
possibility of stopping drug treatment, 259
present status, 254
prognosis, 10, 11, 13
relapse, 197, 257
Rowley’s work, 37
See also Gleevec; Philadelphia chromosome
Ciba-Geigy, 105, 106, 107, 110, 115, 116, 119, 120, 122, 128, 137, 138, 142, 143, 150, 151, 153, 156
cisplatin, 109
clinical trial protocol, 152, 262
CLL. See chronic lymphocytic leukemia
cloning
Abelson virus, 77
cancer research and, 64, 81, 82
fear of, 81
invention, 49
viruses, 49
CML. See chronic myeloid leukemia
Cohen, Sir Philip
about, 122
career, 46
research, 46, 47, 54, 86, 100
Cohen, Stanley, 50
colchicine, 36
Collett, Marc, 46, 50, 64, 88
constitutively active, 86
corticosteroids, 59
Crick, Francis, 158
crizotinib, 268
cyclic-dependent kinase inhibitors, 266
cytogenetic response, 183, 197, 211, 268
cytogenetics, 35, 36
D
Daley, George, 127, 129
Dalton, Jack, 58
Dana-Farber Cancer Institute, 92, 95, 97, 115, 117, 130, 131, 133, 137, 156, 163, 216
dasatinib, 257, 258
death, coping with, 97
deletions, 22, 38
Demetri, George, 247
Dinex, 105
disease
DNA and, 15
genes and, 35
genetic abnormalities and, 82
DNA
genetic code, 29
personal genome sequencing, 261, 265, 269
recombinant DNA, 49, 50, 76, 81, 82, 88
RNA and, 29
structure,15
tumor sequencing, 261, 265
DNA viruses, 28, 29
Doolittle, Russell, 52
Douaze, Pierre, 164
Down syndrome, genetic abnormalities and, 16, 82
Dreger, Suzanne, 234
drug candidate testing, 113, 114, 117
CGP-57148B, 138
drug development
in 1970s, 104
academia-industry collaboration, 262
animal testing, 152
Bayh-Dole Act, 263
Ciba-Geigy in mid 1980s, 107
clinical trial protocol, 152
discovery team vs. development team, 148
investigational new drugs, 142
kinase inhibitors of the future, 266
limited market for a new drug, 142, 145, 169
rational drug design, 108, 112, 266
testing combinations of experimental drugs, 264
testing drug candidates, 113, 114, 117
See also cancer treatment
drug resistance, 248, 257, 267
drugs
delivery systems, 148
FDA approval, 214
generic drugs, 156
marketing, 233
names of, 231
orphan drugs, 229, 254
Druker, Brian
in 1990s, 131
about, 116, 117, 146, 149, 150, 151, 200
academia-industry collaborations, 262
and animal testing of drug, 152
awards, 238, 245
Beth Israel Hospital (Boston), 134
Blueprint Medicine, 269
on cancer treatment, 269
career, 90, 91, 95, 101, 116, 129, 133, 238, 245, 269
career goals, 135
CGP-57148B drug candidate testing, 138
and clinical trials of CGP-57148B, 154
at Dana-Farber, 95, 103, 133, 137
Dana-Farber/Sandoz agreement and, 131
drug shortage for phase II study, 208, 217
Eichner’s treatment and, 4, 5
FDA approval announcement, 234
financial reward from Gleevec, 245
Ford and, 153, 155
4G10 antibody, 103, 116, 117
on genetic profiling, 268
Lydon and, 118, 129, 131, 137, 165
marrow-cleaning approach, 144
Matter and, 131, 163
medical school, 51, 56
at Nashoba Community Hospital, 101, 106, 129, 132, 136
at Novartis, 157, 160, 164
as oncology fellow, 98
personal life, 103, 129, 131, 135, 225, 239
phase I clinical trial, 146, 154, 171, 175
phase II clinical trial, 196, 198, 201, 215, 216
phase III clinical trial (IRIS), 201, 219, 233, 247, 253, 255
post-approval travels, 238
present research funding, 245
presentation of phase I study to ASH (1999), 208, 210, 213
recognition by Novartis, 236, 245
research, 127, 131, 137, 138, 252, 261
as runner, 136, 203, 217
wall of patient photos, 217
Dulbecco, Renato, 30
E
EGFR (epidermal growth factor receptor), 106, 114, 118, 123
Egroup.com, 200, 205
Eichner, Gary, 4, 270
The Emperor of All Maladies (Mukherjee), 265
Encyclopedia of DNA Elements (ENCODE), 33
environmental factors, turning normal gene into oncogene, 50
erbstatin, 123
Erikson, Ray
about, 31, 50
career, 31, 32
research, 32, 40, 45, 58, 64, 68, 69, 72, 88
erlotinib, 265
Escherichia coli, active kinase produced from, 113
estrogen, 132
Europe, Gleevec approval in, 253, 254
“expanded access” trial, 220, 227
F
FDA
accelerated approval, 214, 215, 230
conditional approval, 262
fast-track designation, 215, 230
full approval, 262
orphan drug status, 229
reconfiguring approval process, 262
FDA review of STI-571, 214, 227, 230
FISH (fluorescence in situ hybridization), 144
flag methyl, 126
flavones, 124
focus assay, 28, 30, 58
Folkman, Judah, 158
Ford, Joh
n, 146, 151, 153, 155, 159, 169, 177, 188
4G10 antibody, 103, 116, 117
Franklin, Rosalind, 158
Freireich, Emil, 21
Friedrich Miescher Institute (FMI), 110
G
gag/abl fusion gene, 83
Gag/Abl fusion kinase, 78, 83
Gag/Abl protein, 63, 72, 85, 112
CML and, 79, 80
Gag antibody, 71, 85
gag gene, 72
Gag protein, 70, 71, 85
gastrointestinal stromal tumors (GIST), 247, 253, 266
gel electrophoresis, 71, 112
Genentech, 50
generic drugs, 156
generic names, 231
genes
about, 15
change into cancer-causing genes, 43
deletions, 22, 38
disease and, 35
See also entries for specific genes
genetic abnormalities, diseases linked to, 82
genetic code, 29
genetic testing, 134
genetics, 34
in 1959, 15
cloning, 49, 64, 77, 81
oncogene capture, 44, 60, 78
overexpression, 106
transformation system, 67, 68, 69, 71, 89
translocation, 39, 81, 84
See also mutations
genome sequencing, 261, 265, 269
Giemsa staining, 33
Gilboa, Eli, 77
GIST (gastrointestinal stromal tumors), 247, 253, 266
Gleevec (imatinib mesylate) (Novartis), xii, 232
for brain tumors, 247
for children, 254
cost to patient, 243, 259, 265
FDA approval news conference, 234
FDA conditional approval, 232, 234
FDA standard approval, 254
for GIST, 247, 253
international approvals, 253
international use, 264
length of patients’ responses, 255
package insert, 232
patent expiration, 258, 265
possibility of stopping drug treatment, 259
resistance, 248, 257, 267
sales figures, 245, 254, 265
second-generation tyrosine kinase inhibitors, 258, 268
side effects, 248
sliding scale assistance program, 244
survival data, 267
treatment continued indefinitely, 256
See also STI-571
glioblastoma multiforme, 163
Glivec, 230, 231, 254
glucose metabolism, kinases and, 47, 48
Glyset, 231
Goff, Stephen
about, 28, 30, 71, 77, 78, 88
career, 27, 70, 71, 76
research, 27, 74, 76
Goldman, John, 150, 152, 181, 203, 216, 237
gout, Ilaris for, 255
Graf, Peter, 153, 155, 180
Gratwohl, Alois, 146, 151, 177
Graziani, Yosef, 123
Griffin, Jim, 130, 133, 139
Groffen, John, 81, 82, 85, 88, 118
Grosveld, Gerard, 83, 118
H
hairy cell leukemia, 105, 268
Hanafusa, Hidesaburo, 30, 42
Hardy, Alexandra, 158, 224, 239
Hatch-Waxman Act, 156
Heisterkamp, Nora, 81, 82, 85, 88, 118
hematologic malignancies, 20
hematologic response, 183, 211
Hemmings, Brian, 48, 111, 127
hemophilia, genetic abnormalities and, 82
HER2, 187
Herceptin, 132, 187, 266
Hidaka, Hiroyoshi, 110, 123
Hodgkin’s disease, 97
Howard Hughes Medical Institute, 245
human genome, 15, 33
Human Genome Project, 33, 34
Hunger, Tony, 53
Hungerford, Alice, 16, 22
Hungerford, David
about, 19, 58, 63
death, 24
discovery of Philadelphia chromosome, 15, 16, 83
early career, 20, 58
later career, 23
Hunter, Tony
career, 53
research, 53, 55, 58, 69, 73, 88, 89, 92, 99
Hydrea (hydroxyurea), 185
hypotonic solution, 16, 17
I
Iclusig (ponatinib), 260
Ilaris (drug), 255
imatinib mesylate (Gleevec) (Novartis), 230
See also STI-571
immunostimulants, 105
India, Gleevec used in, 265
industry-academia collaborations, 117, 130, 262
insulin, 47, 48
insurance coverage, and Gleevec, 243
interferon, 105, 181
for CML, 105, 189, 191, 205, 219, 243
cost of, 243
International Randomized of Interferon and STI-571 (IRIS), 219, 247
side effects, 192
Internet chat, phase I patients, 199
investigational new drug (IND) approval, 154, 165, 169, 264
IRIS (International Randomized Study of Interferon and STI-571) (phase III), 219, 247, 253, 255
See also phase III clinical trial
isoflavones, 124
isoquinolinesulfonamides, 110, 123
J
JAK1, 266
JAK2, 266
Japan, Gleevec approval in, 254
K
K562, 86
kidney cancer, 266
kinase inhibition, 108, 115, 122, 128, 129, 137, 158, 169
new drug development, 265, 266
second-generation drugs, 258, 261, 268
kinases
abl oncogene, 78
binding site, 122
cancer and, 89, 92, 106, 118
in cellular processes, 51
constitutively active, 86
determining target of, 54
drug resistance and, 252, 257, 267
early research, 46, 50, 51, 54, 73
encoded by proto-oncogenes, 89
Gag/Abl fusion kinase, 78, 83
in glucose metabolism, 47, 48
overexpression, 106
produced from E. coli, 113
for rational drug design, 108, 112, 266
Kinetix, 157
Kipnis, David, 91, 92, 97
Kit, 163, 247
Klausner, Richard, 234, 235, 236, 247
Klinefelter’s syndrome, genetic abnormalities and, 82
Knight, Phil, 246
Knight Cancer Institute, 246
Kobilka, Brian, 90
Kuriyan, John, 251
L
lapatinib, 266
Lawce, Helen, 144
leukemia, 152, 191
oncogene causing, 88
Philadelphia chromosome in, 22
translocations and, 39, 81
treatment methods involving bone marrow, 143
types, 19
Leukemia and Lymphoma Society, 246
Levan, Albert, 36
Levinson, Art, 46
Levitzki, Alexander, 122, 124, 142
Li-Fraumeni syndrome, 134
Lichtenfeld, J. Leonard, 267
liquid cancers, 20, 150
Livingston, David, 133
Loland, Hans, 260
lung cancer, 106, 265, 268
Lydon, Nick
about, 89, 110, 111, 115, 127, 129, 140, 141, 145, 146, 148, 149, 150, 151, 157, 237, 249, 263
awards, 238, 245
Blueprint Medicine, 269
career, 48, 56, 89, 105, 107, 111, 115, 117, 137, 157, 269
Druker and, 118, 129, 131, 137, 165
Kinetix, 157, 166
research, 89, 104, 106, 111, 113, 118, 127, 128, 130, 138, 163
lymphocytes, 61
lymphocytic leukemia, Moloney virus and, 60
lymphomas, 20
lymphosarcoma, 61, 62
M
Magic Cancer Bullet (Vasella & Slater), 237
Martin, G. Steven, 31, 42
material transfer agreements, 117
Matter, Alex
about, 56, 115, 141, 145, 148, 149, 151, 159, 160, 237, 258
career, 104, 106, 107, 115, 164
at Ciba-Geigy, 106, 107, 113, 115, 119, 120
Druker’s letter to, 165, 166, 168
at Novartis, 163, 164
research, 106, 109, 113, 119, 127, 138, 163, 258
Vasella and, 167
Zimmermann and, 121
Mauro, Michael, 218, 259, 260, 264, 268, 271
Mayer, Thomas, 110, 124
McNamara, Suzan, 205, 208, 216, 271
Medicare, coverage of cancer treatment, 243
MEK, 266
melanoma, 105
message boards, phase I patients, 199
N-methylpiperazine, 128
Mett, Helmut, 110
midde T kinase, 55
“middle T,” 53
Moloney virus, 59, 70, 76
Morrison, Deborah, 102
Mukherjee, Siddhartha, 265
Mulder, Gerrit, 45
multiple myeloma, 20
mutations, 22
in CML, 15, 17, 83, 252, 260, 267
constant appearance of new mutations, 267
drug resistance and, 252, 267
hairy cell leukemia, 268
spontaneous mutations, 191
T315, 260
temperature-sensitive mutations, 31, 40
tumor sequencing, 261, 265
myc gene, 50
N
Nashoba Community Hospital, 101, 106, 129, 132, 136
National Institutes of Health (NIH), 57, 59
Neil, Robert, 200
NIH. See National Institutes of Health
nilotinib, 258
Nishizuka, Yasutomi, 106
Novartis
animal studies, 158, 170
Capdeville, 213
Douaze as interim CEO, 164
drug supply shortage, 201, 202, 203, 205, 208, 209, 217
earnings from Gleevec, 244
“expanded access” trial, 220, 227
Ford at, 146, 151, 153, 155, 159, 169
formation, 156
Gleevec, FDA approval announcement, 234
Gleevec patent, 258, 265
marketing of Gleevec, 33
McNamara online petition, 206, 208
orphan drugs from, 254
patent fight in India, 265
pill formulation, 158
recognition of Druker, 236, 245
reconfigured testing and FDA approval process, 262
second-generation tyrosine kinase inhibitors, 258
sliding scale assistance program, 244, 259
STI-571 production expedited, 209, 213
toxicity concerns, 160, 163, 164, 169, 171, 179, 211, 233
Vasella as CEO, 167, 168, 169, 203, 206, 209, 213, 234, 236, 244, 258
Nowell, Peter
about, 19, 58
career, 19, 23, 58
discovery of Philadelphia chromosome, 16, 83
nucleotide sequences, alterations in, 34
nucleotides, 29
O
octreotide, 167
O’Dwyer, Michael, 216, 218
onco-proteins, 51
oncogene capture, 44, 60, 78
oncogene hypothesis, 41, 42
oncogenes, xi, 49, 60
The Philadelphia Chromosome Page 32