K
karyotype:
A photomicrograph of an individual's complete set of chromosomes
arranged in homologous pairs and ordered by size. Karyotypes show the
number, size, shape and banding pattern of each chromosome type. They
can be used to determine if there are large abmormalities in the
chromosomes, such as a major deletion, insertion or translocation.
knockout mouse:
A mouse that has had both alleles of a particular gene replaced with an
inactive allele, usually through homologous recombination. Knockout
mice are used to determine the role of a particular gene by observing
the phenotype of individuals that lack the gene completely.
L
leukocytes: White blood cells.
ligand:
A linking or binding molecule that binds to a specific complementary
site on (forms a complex with) another molecule. For example, a growth
factor is a ligand for its growth factor receptor.
leukemia: Cancer of white blood cells.
Li-Fraumeni syndrome:
A rare, inherited familial cancer syndrome characterized by tumors at
multiple sites. A mutation of the p53 tumor suppressor gene predisposes
family members who inherit it to develop multiple cancers.
LTFU: Long-term follow up.
lumen: The inner cavity or open space of a tube or tubular organ (e.g., blood vessel, intestine).
lymphocyte:
White blood cells that kill viruses and defend against the invasion of
foreign material. These cells mediate the specificity of immune
responses. See B cell and T cell.
lymphoma: Cancer of lymphocytes or the lymphoid system (e.g., Hodgkin's disease, non-Hodgkin's lymphoma).
M
metastasize:
To spread from one part of the body to another. When cancer cells
metastasize and form secondary tumors, the cells in the metastatic
tumor are like those in the original (primary) tumor.
MHC (major histocompatibility complex) molecules:
Highly variant (or polymorphic) molecules expressed on the surface of
most cells that flag the cell as "self" and present foreign antigens to
T cells. These pitchfork-shaped molecules mediate cellular interactions
in the immune system by displaying antigens on the cell surface and are
also responsible for rapid rejection of grafts between individuals. In
humans, MHC molecules are also called HLA antigens.
mitosis: The process of cell division, resulting in formation of two daughter cells that are genetically identical to the parent cell.
multidrug resistance:
The ability of a tumor cell to develop resistance to a number of
structurally and functionally unrelated drugs, following exposure to a
single agent.
murine (mouse) antibody: The antibody is derived solely from mouse proteins and is viewed as foreign by the host (human) body.
mutation:
A heritable change in the sequence of the DNA. Mutations can result
from errors in DNA replication or from DNA damage and can range from
changes in a single base pair (point mutation) to gross changes in a
chromosome (duplication, translocation, inversion, deletion). Not all
mutations are harmful—some occur in regions of DNA that do not encode a
gene, and some occur in a gene but do not change the function of the
gene or the eventual amino acid sequence of the protein. Mutations in
the DNA of somatic cells will be passed on to the daughter cells during
cell division. Mutations in the DNA of a gamete will be inherited by
subsequent generations of offspring. Also called a genetic change.
myeloma: Cancer of the bone marrow, especially the antibody producing cells in the bone marrow.
N
National Cancer Institute (NCI):
Part of the National Institutes of Health of the United States
Department of Health and Human Services, the NCI is the federal
government's principal agency for cancer research. NCI conducts,
coordinates and funds cancer research, training, health information
dissemination and other programs with respect to the cause, diagnosis,
prevention and treatment of cancer. Access the NCI website at
www.cancer.gov.
natural killer (NK) cell: A cytotoxic cell of the immune system that can recognize and destroy a large variety of virally infected cells and tumor cells.
neoadjuvant:
Initial treatment which is not the primary therapy (for instance,
chemotherapy or radiation, prior to surgery). It is often administered
in instances of locally advanced disease in the hope that the size of
the tumor is reduced in order that it might be surgically removed.
neoplasm: An abnormal new growth of tissues or cells. Neoplasms can be benign or malignant.
New Drug Application (NDA):
The vehicle through which drug sponsors formally propose that the U.S.
Food and Drug Administration approve a new pharmaceutical for sale and
marketing. This application is usually filed once a trial has generated
adequate data to support a certain indication for a drug (usually by
finding that the drug is safe and superior to standard treatment in a
definitive phase III trial). The data gathered during pre-clinical
studies as well as manufacturing specifications of an Investigational
New Drug are also part of the NDA filing.
non-Hodgkin's lymphoma:
A group of cancers of the lymphoid system, including acute
lymphoblastic leukemia, B-cell lymphoma, Burkitt's lymphoma, diffuse
cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma,
lymphoblastic lymphoma, mantle cell lymphoma, mycosis fungoides,
post-transplantation lymphoproliferative disorder, small non-cleaved
cell lymphoma and T-cell lymphoma.
non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma.
nucleotides:
The building blocks of nucleic acids (DNA and RNA). The four nucleotide
bases are guanine (G), cytosine (C), adenine (A) and thymine (T).
nucleus: The part of the cell bounded by its own nuclear membrane that contains the chromosomes.
O
Office for Human Research Protections (OHRP):
This office safeguards participants in federally-funded research and
provides unity and leadership for many federal departments and agencies
that carry out research involving human participants.
oncogene:
A mutated proto-oncogene that is locked into an active state and
continuously stimulates unregulated cell growth and proliferation that
leads to tumor development. Myc, ras and erb are examples of oncogenes.
The normal allele of an oncogene is called a proto-oncogene.
oncogenesis:
The process by which normal cells turn cancerous. A sequence of
cytological, genetic and cellular changes causes the formation and
development of tumors. Also called tumorigenesis.
oncology: The branch of medicine that deals with tumors, including study of their development, diagnosis, treatment and prevention.
overall survival: The percentage of subjects in a study who have survived for a defined period of time. It is usually reported as a hazard ratio.
P
P-glycoprotein: The first identified and best studied of the ABC drug transporters.
p-value:
A measure of probability that a difference between groups during an
experiment happened by chance. For example, a p-value of .01 (p=.01)
means that there is a 1 in 100 chance the result occurred by chance.
The lower the p-value, the more likely it is that the difference
between groups was caused by treatment.
palliative treatment: Treatment aimed at the relief of pain and symptoms of disease but is not intended to cure the disease.
partial response:
A decrease in the size of a tumor, or the regression by more than 50
percent but less than 100 percent of the extent of cancer in the body.
pathogenesis: The development of disease.
pharmacogenetics:
The study of the genetic factors that influence each person's reaction
to a drug. Pharmacogenetic studies are helping to advance the concept
of personalized medicine, in which anticancer treatments will be
tailored to the individual patient based on his or her genetic,
epigenetic and proteomics profiles.
phase I trial: Small
groups of people with cancer are treated with a certain dose of a new
agent that has already been extensively studied in the laboratory.
During the trial, the dose is usually increased group by group in order
to find the highest dose that does not cause harmful side effects. This
process determines a safe and appropriate dose to use in a phase II
trial. Usually does not include a control treatment for comparison.
phase II trial:
Phase II trials continue to test the safety of the new agent and begin
to evaluate how well it works against a specific type of cancer. In
these trials, the new agent is given to groups of people with one type
of cancer or related cancers, using the dosage found to be safe in
phase I trials. Usually the new agent is compared with a standard
treatment in this type of trial.
phase III trial: Phase
III studies are designed to answer research questions across the
disease continuum. Phase III trials usually have hundreds to thousands
of participants, in order to find out if there are true differences in
the effectiveness of the treatment being tested. Once this phase is
completed, the pharmaceutical company will usually submit a New Drug
Application to the FDA, provided the results of the trials warrant such
a request.
phase IV trial: Phase IV trials are used to
evaluate the long-term safety and effectiveness of a treatment. Less
common than phase I, II, and III trials, phase IV trials take place
after the new treatment has been approved for standard use.
phenotype:
The observable physical and biochemical characteristics or traits of an
organism such as hair color, blood type, or the presence or absence of
a disease. The phenotype is determined by both genetic and
environmental influences.
Pilot 1: Under the FDA's
Continuous Marketing Approval program, the Pilot 1 program allows
applicants submitting New Drug Applications (NDAs) to submit portions
of their marketing applications (reviewable units) before submitting
the complete marketing application. The FDA has agreed to complete
reviews of these reviewable units within a specified period of time and
to provide early feedback for the pre-submissions. Pilot 1 also will
evaluate the benefits and costs of providing applicants with such early
review feedback.
pivotal trial: A controlled trial to
evaluate the safety and efficacy of a drug in patients who have the
disease or condition to be treated. These trials usually represent the
most rigorous demonstration of the therapeutic's efficacy and safety,
and are the basis for the NDA filing with the FDA.
placebo-controlled:
Refers to a clinical study in which the "control" patients receive a
placebo, or inert medication or procedure. The experience of the
control group of patients is compared with that of the patients who
received the investigational drug to determine the safety and efficacy
of the therapy being studied.
preclinical testing: A
process in which scientists test promising new anticancer agents in the
laboratory and in animal models. This is done to find out whether
agents have an anticancer effect and are safely tolerated in animals.
Once a drug proves promising in the lab, the sponsor applies for Food
and Drug Administration approval to test it in clinical trials
involving people.
prevention trials: Trials involving
healthy people who are at high risk for developing cancer. These trials
try to answer specific questions about and evaluate the effectiveness
of ways to reduce the risk of cancer.
principal investigator (PI): The person, usually a doctor, who is in charge of a clinical trial. The PI prepares a protocol for the trial.
priority review:
A designation for an application after it has been submitted to the FDA
for review for approval of a marketing claim. Under the Food and Drug
Administration Modernization Act (FDAMA), reviews for New Drug
Applications are designated as either Standard or Priority. A Standard
designation sets the target date for completing all aspects of a review
and the FDA taking an action on the application (approve or not
approve) at 10 months after the date it was filed. A Priority
designation sets the target date for the FDA action at six months. A
Priority designation is intended for those products that address unmet
medical needs.
progression-free survival: This term
defines the length of time during and after treatment that the cancer
does not grow. Progression-free survival includes the amount of time
patients have experienced a complete response or a partial response, as
well as the amount of time patients have experienced stable disease.
progressive disease:
Progressive disease is defined in clinical trials as tumor growth of
more than 20 percent since treatment began. Tumor growth means that the
tumor is getting bigger, but it may also mean that the tumor is
spreading. Progression generally indicates that treatment has stopped
working.
proteome: All of the proteins encoded by the genome and made by a person's cells and tissues.
proteomics:
The study of the networks of proteins within cells and tissues.
Proteomics involves identifying all the proteins made in a cell or
tissue, deciphering how these proteins interact, and determining their
three-dimensional structures to find sites where drugs could interfere
with their function.
protocol: A written plan that acts
as a "recipe" for conducting a clinical trial. The protocol explains
what a trial will do, how it will be carried out, and why each part of
the trial is necessary.
proto-oncogenes: A gene that promotes normal cell growth and differentiation.
Q
quality of life:
The overall enjoyment of life. Many clinical trials measure aspects of
an individual's sense of well-being and ability to perform various
tasks to assess the effects of cancer and its treatment on the quality
of life.
R
radiotherapy: The
use of high-energy radiation from X-rays, neutrons and other sources to
kill cancer cells and shrink tumors. Radiation may come from a machine
outside the body (external-beam radiation therapy) or from materials
called radioisotopes. Radioisotopes produce radiation and can be placed
in or near the tumor or in the area near cancer cells. This type of
radiation treatment is called internal radiation therapy, implant
radiation, interstitial radiation or brachytherapy. Systemic radiation
therapy uses a radioactive substance, such as a radiolabeled antibody,
that circulates throughout the body. Radiotherapy is also called
radiation therapy, irradiation and X-ray therapy.
randomization:
A method used to prevent bias in research. A computer generates
treatment assignments, and participants have an equal chance to be
assigned to one of two or more groups (e.g., the control group or the
investigational group).
randomized clinical trial: A
study in which the participants are assigned by chance to separate
groups that compare different treatments. Neither the researchers nor
the participants can choose which group. Using chance to assign people
to groups means that the groups will be similar and that the treatments
they receive can be compared objectively. At the time of the trial, it
is not known which treatment is best. It is the patient's choice to be
in a randomized trial.
receptor: Proteins that bind to
their specific ligands with high specificity. Receptors act as the
"antenna" of a cell, and transduce signals from the environment outside
the cell to the inside of the cell. When a receptor binds its ligand,
it is said to be activated and often changes shape, which enables it to
interact with different intracellular signaling molecules.
RECIST criteria:
The standard criteria used for performance measurement in solid tumor
clinical trials. The response criteria for evaluation include complete
response (CR), partial response (PR), progressive disease (PD) and
stable disease (SD).
recurrence: The return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared.
refractory: Cancer that has not responded to treatment.
relapse: The return of signs and symptoms of cancer after a period of improvement.
remission:
A decrease in or disappearance of signs and symptoms of cancer. In
partial remission, some, but not all, signs and symptoms of cancer have
disappeared. In complete remission, all signs and symptoms of cancer
have disappeared, although there still may be cancer in the body.
response rate: The percentage of patients whose cancer shrinks more than 50 percent following treatment.
RNA (ribonucleic acid):
A single-stranded nucleic acid containing ribose instead of
deoxyribose. Messenger RNA (mRNA) is formed on and complementary to its
DNA template and directs the translation of a gene into a protein.
S
sarcoma: Cancer of muscles or connective tissues such as bone, cartilage and fat.
second-line treatment:
Treatment that is given after the cancer has not responded to a first
course of therapy or a patient ceases first-line of therapy.
sequelae: A pathological condition resulting from a disease, or a secondary consequence or result.
signal transduction:
Usually refers to the series of steps that occurs in the cell cytoplasm
after a receptor has bound its ligand to communicate/transduce the
signal to the cell nucleus. The "signal" of an activated receptor is
carried through the cells by various intracellular messengers and
cascades of enzymes. Often the signal will be sent to the nucleus,
where genes are turned on and/or off to change the function of the
cell. Sometimes referred to as downstream signaling.
small cell lung cancer:
A type of lung cancer in which the cells appear small and round when
viewed under the microscope. About 20 percent of all lung cancers are
SMLC.
somatic cell: All cells in the body except the
gametes. Mutations in the DNA of somatic cells is passed on to the
daughter cells during cell division, but is not inherited by the
organism's offspring.
squamous cell carcinoma: Cancer
that begins in squamous cells, which are thin, flat cells resembling
fish scales. Squamous cells are found in the tissue that forms the
surface of the skin, the lining of the hollow organs of the body, and
the passages of the respiratory and digestive tracts.
stable disease:
A tumor may shrink, but not enough to be categorized as a partial
response (that is, tumor reduction greater than 50 percent). Or a tumor
may increase in size, but not enough to be considered progressive
disease (that is, tumor growth greater than 20 percent). Such tumors,
in which there is no significant change in size, are classified as
stable disease.
stage: The extent of a cancer, especially
whether the disease has spread from the original site to other parts of
the body. The stages of cancer vary for each cancer type and with the
staging system used. Generally, cancers can be classified as:
stage 0: The stage where the cancer is still confined to the tissue in which it started. Also called cancer in situ.
stage 1: The tumor is larger than in stage 0, but still localized.
stage 2: The tumor is larger, and cancer cells may be present in nearby lymph nodes.
stage 3: Cancer has spread to nearby lymph nodes and/or tissue.
stage 4: Cancer has spread to distant lymph nodes and/or organs.
standard treatment:
A currently accepted and widely used treatment for a certain type of
cancer, based on the results of past research. Also known as standard
therapy.
stroma: The nonmalignant host cells and extracellular matrix in which a tumor grows.
symptom deterioration: A deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression.
T
T cell or T-lymphocyte:
White blood cells responsible for generating cell-mediated immune
responses. Some T cells (helper T cells) enhance the response of other
effector cells, including B cells, macrophages and NK cells, by
secreting cytokines. Others (cytotoxic T cells) can directly kill
virus-infected cells and tumor cells. T cells are antigen-specific, but
unlike antibodies they only recognize their antigen when it is cut into
tiny pieces that are loaded into MHC molecules and displayed on the
surface of a cell.
targeted therapy: A type of treatment
that uses drugs or other substances to identify and attack specific
cancer cells while limiting affect on normal cells.
telomeres:
Special DNA sequences at the ends of each chromosome that grow shorter
each time a cell divides. Telomeres count the number of cell divisions,
and when it shortens to a certain length, the cell will stop dividing
(senescence) and eventually die.
telomerase: An enzyme
that rebuilds telomeres. Telomerase is overexpressed in many cancer
cells, and contributes to their immortality, or ability to divide
endlessly.
third-line treatment: Treatment that is given
after the cancer has not responded to a second course of therapy or a
patient ceases second-line of therapy.
toxicity: Harmful side effects from an agent being tested.
transformation: The process by which a normal cell undergoes a series of changes that cause it to become cancerous.
transcription:
The synthesis of a single stranded, complementary RNA molecule from a
DNA template in the cell nucleus. When a gene is transcribed, it is
said to be expressed. Not all genes are expressed in all cells.
transcription factors:
Proteins that bind to DNA and help initiate gene transcription.
Transcription factors are often important elements of signal
transduction pathways.
transgenic mouse: A mouse that has
had DNA artificially introduced into one or more of its cells.
Transgenic mice are often used to examine the effects of overexpressing
or misexpressing a normal or mutated gene at a specific time and/or in
specific tissue.
translation: The synthesis of a polypeptide chain (protein) from its mRNA template.
translational research:
Research that bridges the gap between laboratory research and its
application to the clinic. This type of research, which often involves
teams of scientists, conveys new ideas and discoveries between the lab
and clinic both to increase our understanding of cancer and to advance
the areas of diagnosis, treatment and prevention of cancer.
translocation: An abnormal rearrangement of the DNA in a chromosome.
tumor:
An abnormal mass of tissue that results from excessive cell division.
Tumors perform no useful body function. They may be benign (not
cancerous) or malignant (cancerous).
tumor suppressor gene:
A gene that normally inhibits excessive cell proliferation. Mutations
that permanently disable tumor suppressor genes can cause a cell to
grow uncontrollably, leading to tumor development. Examples of tumor
suppressors are pRB and p53. pRB (retinoblastoma protein) regulates the
cell cycle at cell cycle checkpoints. p53 regulates the activity of
certain molecules involved in the cell cycle. It also prevents DNA
replication and cell division in normal cells with damaged DNA.
tumorigenesis: See "oncogenesis".
tyrosine kinases: A large group of enzymes important in cell growth, differentiation and development.
V
vaccine:
A substance or group of substances meant to cause the immune system to
respond to a tumor or to microorganisms, such as bacteria or viruses.
VEGF (vascular endothelial growth factor):
A protein that is secreted by oxygen-deprived cells, such as cancerous
cells. VEGF stimulates new blood vessel formation, or angiogenesis, by
binding to specific receptors on nearby blood vessels, encouraging new
blood vessels to form.
virus: A very small infectious
agent that carries proteins and nucleic acids (DNA or RNA) in a
protective coat. After infecting a cell (also called a host cell) and
injecting its genetic material inside the host, a virus may lie dormant
(inactive) for a length of time. Viruses depend on the host cells to
survive; infected cells act as virus-making factories. Viruses
contribute to the etiology of certain cancers. See infection. They are
also used as vectors (vehicles or tools) to deliver drugs or carry
genes for gene therapy.
W-Z
white blood cells: A variety of cells that fight invading germs, infection and allergy causing agents. Also called leukocytes.
This glossary was compiled by scientific mentors of the Scientist↔Survivor Program®
and AACR staff. The definitions used were provided by the mentors and
AACR staff, or were adapted from Alberts B, Bray D, Lewis J, Raff M,
Roberts K, and Watson JD. Molecular Biology of the Cell
, 2nd
Edition, New York: Garland Publishing Inc., 1989, or were adapted or
copied directly from the NCI website's Dictionary of Cancer Terms (www.cancer.gov/dictionary), Medicine OnLine's Cancer Glossary (www.meds.com/glossary.html), Merriam Webster's Collegiate Dictionary: 11th Edition
, or the American Heritage
® Dictionary of the English Language: Fourth Edition
, 2000.
July 7, 2006