Cancer therapeutics

1. CANCER
Cancer is a group of more than 100 different diseases that are
characterized by uncontrolled cellular growth, local tissue
invasion, and distant metastases. .
The four most common cancers are prostate, breast, lung, and
colorectal cancer. The most common cause of cancer-related
deaths in the United States is lung cancer.
The roles of healthcare professionals in the management of
cancer patients can be very diverse. Thorough knowledge of
antineoplastic drug pharmacology and pharmacokinetics is
essential to prevent and to manage drug-induced toxicities.
Supportive-care issues, such as nutritional support, pain
management, infection, and nausea and vomiting, require
application of clinical, pharmacologic, and economic
principles.

3. ETIOLOGY OF CANCER
CARCINOGENESIS A cancer, or neoplasm, is thought to develop
from a cell in which the normal mechanisms for control of
growth and proliferation are altered.
Current evidence supports the concept of carcinogenesis as a
multistage process that is genetically regulated.
The first step in this process is initiation, which requires exposure of
normal cells to carcinogenic substances. These carcinogens
produce genetic damage that, if not repaired, results in
irreversible cellular mutations.
This mutated cell has an altered response to its environment and a
selective growth advantage, giving it the potential to develop into
a clonal population of neoplastic cells.
During the second phase, known as promotion, carcinogens or other
factors alter the environment to favor growth of the mutated cell
population over normal cells.

4. The primary difference between initiation and promotion is that
promotion is a reversible process. Because it is reversible, the
promotion phase may be the target of future chemoprevention
strategies, including changes in lifestyle and diet. At some
point, however, the mutated cell becomes cancerous
(conversion or transformation).
The final stage of neoplastic growth, called progression,
involves further genetic changes leading to increased cell
proliferation. The critical elements of this phase include tumor
invasion into local tissues and the development of metastases.

5. Substances that may act as carcinogens or initiators include chemical, physical, and
biologic agents.
Exposure to chemicals may occur by virtue of occupational and environmental
means, as well as lifestyle habits.
The association of aniline dye exposure and bladder cancer is one such example.
Benzene is known to cause leukemia.
Some drugs and hormones used for therapeutic purposes are also classified as
carcinogenic chemicals (Table 130–1).
Physical agents that act as carcinogens include ionizing radiation and ultraviolet
light.
These types of radiation induce mutations by forming free radicals
that damage DNA and other cellular components.
The Epstein-Barr virus is believed to be an important factor in the initiation of
Burkitt’s lymphoma. Likewise, infection with human papilloma virus is known
to be a major cause of cervical cancer.
All the previously mentioned carcinogens, as well as age, gender, diet, growth
factors, and chronic irritation, are among the factors considered to be promoters
of carcinogenesis.

7. GENETIC AND MOLECULAR BASIS OF CANCER
Two major classes of genes are involved in carcinogenesis: oncogenes and
tumor suppressor genes. Figure 130–2 illustrates the acquired capabilities
of cancer cells that differ from normal cellular function.
Oncogenes develop from normal genes, called protooncogenes, and may have
important roles in all phases of carcinogenesis.
Protooncogenes are present in all cells and are essential regulators of normal
cellular functions, including the cell cycle.
These genetic alterations may be caused by carcinogenic agents such as
radiation, chemicals, or viruses (somatic mutations), or they may be
inherited (germ-line mutations). Once activated, the oncogene produces
either excessive amounts of the normal gene product or an abnormal gene
product.

8. The result is dysregulation of normal cell growth and
proliferation.
An example is the human epidermal growth factor receptor
(HER) family of oncogenes. This family of receptor tyrosine
kinases contains four members: ErbB-1, also known as
epidermal growth factor receptor (EGFR), HER-2, HER-
3, and HER-4.
When activated, these receptors mediate cell proliferation and
differentiation of cells through activation of intracellular
tyrosine kinase receptors and downstream signaling pathways.
As an oncogene, the gene product is overexpressed or amplified,
resulting in excessive cellular proliferation, metastasis,
angiogenesis, and cell survival in several cancers. Table 130–2
lists examples of oncogenes by their cellular function.

10. In contrast, tumor suppressor genes regulate and inhibit inappropriate
cellular growth and proliferation.
Gene loss or mutation results in loss of control over normal cell
growth.
Two common examples of tumor suppressor genes are the
retinoblastoma and p53 genes.
The normal gene product of p53 is responsible for negative regulation
of the cell cycle, allowing the cell cycle to halt for repairs,
corrections, and responses to other external signals.
Inactivation of p53 removes this checkpoint, allowing mutations to
occur.
Mutation of p53 is linked to a variety of malignancies, including brain
tumors (astrocytoma); carcinomas of the breast, colon, lung, cervix,
and anus; and osteosarcoma. Another important function of p53
may be modulation of cytotoxic drug effects.
Loss of p53 is associated with antineoplastic drug resistance.

11. Another group of genes important in carcinogenesis are the DNA
repair genes.
The normal function of these genes is to repair DNA that is
damaged by environmental factors, or errors in DNA that
occur during replication.
If not corrected, these errors can result in mutations that activate
oncogenes or inactivate tumor suppressor genes.
The DNA repair genes have been classified as tumor suppressor
genes because a loss in their function results in increased risk
for carcinogenesis.
Deficiencies in DNA repair genes have been discovered in
familial colon cancer (hereditary nonpolyposis colon cancer)
and breast cancer syndromes.

12. Oncogenes and tumor suppressor genes provide the stimulatory
and inhibitory signals that ultimately regulate the cell cycle.
These signals converge on a molecular system in the nucleus
known as the cell-cycle clock.
The function of the clock in normal tissue is to integrate the
signal input and to determine if the cell cycle should proceed.
The clock is composed of a series of interacting proteins, the
most important of which are cyclins and cyclin-dependent
kinases.
Cyclins (especially cyclin D 1 ) and cyclin-dependent kinases
promote entry into the cell cycle and are overexpressed in
several cancers, including breast cancer.
Cyclin-dependent kinase inhibitors have been identified as
important negative regulators of the cell cycle.

13. When the normal regulatory mechanisms for cellular growth fail, backup defense systems
may be activated.
The secondary defenses include apoptosis (programmed cell death or suicide) and cellular
senescence (aging).
Apoptosis is a normal mechanism of cell death required for tissue homeostasis.
This process is regulated by oncogenes and tumor suppressor genes and is also a mechanism
of cellular death after exposure to cytotoxic agents.
Overexpression of oncogenes responsible for apoptosis may produce an “immortal” cell,
which has increased potential for malignancy.
The bcl-2 oncogene is an example.
The most common chromosomal abnormality found in lymphoid malignancies is the
t(14;18) translocation.
The bcl-2 protooncogene is normally located on chromosome 18.
Translocation of this protooncogene to chromosome 14 in proximity to the immunoglobulin
heavy chain gene leads to overexpression of bcl-2, which decreases apoptosis and
confers a survival advantage to the cell.
Studies show that p53 is also a regulator of apoptosis. Loss of p53 disrupts normal apoptotic
pathways, imparting a survival advantage to the cell.

14. Cellular senescence is another important defense mechanism.
Laboratory studies demonstrate that once a cell population has
undergone a preset number of doublings, growth stops and cells
die.
This is known as senescence, a process that is regulated by telomeres.
Telomeres are the DNA segments or caps at the ends of chromo-
somes.
They are responsible for protecting the end of the DNA from damage.
In cancer cells, the function of telomeres is overcome by
overexpression of an enzyme known as telomerase.
Telomerase replaces the portion of the telomeres that is lost with each
cell division, thereby avoiding senescence and permitting an
infinite number of cell doublings.
Telomerase is a target for antineoplastic drug development.

15. As information regarding the role of oncogenes and tumor
suppressor genes accumulated, it became evident that a single
mutation is probably insufficient to initiate cancer.
Early mutations are found in both premalignant lesions and in
established tumors, whereas later mutations are found only in
the established tumor.
This theory of sequential genetic mutations resulting in cancer
has been demonstrated in colon cancer.
In colon cancer, the initial genetic mutation is believed to be loss
of the adenomatous polyposis coli gene, which results in
formation of a small benign polyp.
Oncogenic mutation of the ras gene is often the next step, leading
to enlargement of the polyp.
Loss of function of DNA mismatch repair enzymes may occur at
many points in the progression of malignant transformation.

16. Loss of the p53 gene and another gene, believed to be the
“deleted in colorectal cancer” gene, complete the
transformation into a malignant lesion.
Loss of p53 is thought to be a late event in the development and
progression of the malignancy.
Specific genetic abnormalities are so commonly associated with
some types of cancers that the presence of that abnormality
aids in the diagnosis of that cancer.
If the presence of these genes (i.e., gene expression profile) can
reliably predict the clinical course of a cancer or response to
certain cancer therapies, then genetic analysis may also
become an important prognostic and treatment decision tool.
An example of this is overexpression of HER-2 predicting
response to trastuzumab

17. DIAGNOSIS AND STAGING
SCREENING
Because cancers are most curable with surgery or radiation
before they have metastasized, early detection and treatment
have obvious potential benefits.
In addition, small tumors are more responsive to chemotherapy.
Early diagnosis is difficult for many cancers because they do not
produce clinical signs or symptoms until they have become
large or have metastasized.
Cancer screening programs are designed to detect signs of cancer
in people who have not yet developed symptoms from cancer.

18. • Education of the public on the early warning signs of
common cancers is extremely important for facilitating early
detection.
• For some cancers, effective screening procedures do exist.
• The Papanicolaou (Pap) smear test, for example, is an
effective tool to detect cervical cancer in its early stages. Self-
examination of the breasts in women and of the testicles in
men may lead to early diagnosis of cancers in these organs.
• The American Cancer Society has published guidelines for
routine screening examinations (Table 130–4).13

20. DIAGNOSIS
• The presenting signs and symptoms of cancer vary widely and
depend on the type of cancer.
• The presentation in adults may include any of cancer’s seven
warning signs (Table 130–5), as well as pain or loss of
appetite.
• The warning signs of cancer in children are different, and
reflect the types of tumors more common in this patient
population (Table 130–6).
• Even with increased public awareness, the fear of a cancer
diagnosis can deter patients from seeking medical attention.

21. • The definitive diagnosis of cancer relies on the procurement of
a sample of the tissue or cells suspected of malignancy and
pathologic assessment of this sample.
• This sample can be obtained by numerous methods, including
biopsy, exfoliative cytology, or fine-needle aspiration.
• A tissue diagnosis is essential, because many benign conditions
can masquerade as cancer. Definitive treatment should not begin
without a pathologic diagnosis

23. STAGING AND WORKUP
• In addition to tissue diagnosis, tumors should be staged to
determine the extent of disease before any definitive treatment
is initiated.
• The process is dictated by knowledge of the biology of the
tumor and by the signs and symptoms elicited in the history
and physical examination.
• Staging provides information on prognosis and guides
treatment selection.
• After treatment is implemented, the staging workup is usually
repeated to evaluate the effectiveness of the treatment.
• Uniform staging criteria are imperative in clinical research
aimed at evaluating cancer treatment regimens. Staging has
been valuable in learning more about the biology of various
tumor types.

24. • A staging workup may involve radiographs, computed
tomography scans, magnetic resonance imaging, positron
emission tomography scans, ultrasonograms, bone-marrow
biopsies, bone scans, lumbar puncture, and a variety of
laboratory tests, including appropriate tumor markers.
• Some cancers produce antigens or other substances that are
characteristic of that particular cancer.
• These so-called tumor markers are often nonspecific and may
be elevated in many different cancer types, or in patients with
nonmalignant diseases.
• As a result, tumor markers are generally more useful for
monitoring response and detecting recurrence than as diagnostic
tools.
• Examples are the measure of human chorionic gonadotropin
and alpha-fetoprotein in patients with testicular cancer, or
prostate-specific antigen in prostate cancer

25. • The most commonly applied staging system for solid tumors is the
TNM classification, where T = tumor, N = node, and M =
metastases.
• A numerical value is assigned to each letter to indicate the size or
extent of disease.
• The designated rating for tumor describes the size of the primary
mass and ranges from T1 to T4.
• Carcinoma in situ is designated Tis.
• Nodes are described in terms of the extent and quality of nodal
involvement (N0 to N3). Metastases are generally scored
depending on their presence or absence (M0 or M1).
• To simplify the staging process, most cancers are classified
according to the extent of disease by a numerical system involving
stages I through IV.

26. • Stage I usually indicates localized tumor, stages II and III
represent local and regional extension of disease, and stage
IV denotes the presence of distant metastases.
• The assigned TNM rating translates into a particular stage
classification.
• For example, T3N1M0 describes a moderateto large-sized
primary mass, with regional lymph node involvement and no
distant metastases, and for most cancers is stage III.
• The criteria for classifying disease extent are quite specific for
each different type of cancer. For some tumors, alternative
alphabetical systems (stage A, B, C, or D) are used in clinical
practice.

27. TREATMENT
Modalities of Cancer Treatment
• Four primary modalities are employed in the approach to cancer
treatment: surgery, radiation, chemotherapy, and biologic
therapy.
• The oldest of these is surgery, which plays a major role in the
diagnosis and treatment of cancer.
• Surgery remains the treatment of choice for most solid tumors
diagnosed in the early stages.
• Radiation therapy was first used for cancer treatment in the late
1800s and remains a mainstay in the management of cancer.
• Although very effective for treating many types of cancer, surgery
and radiation are local treatments.
• These modalities are likely to produce a cure in patients with truly
localized disease.

28. • But because most patients with cancer have metastatic disease
at diagnosis, localized therapies often fail to completely
eliminate the cancer.
• In addition, systemic diseases such as leukemia cannot be
treated with a localized modality.
• Chemotherapy (including hormonal therapy) accesses the
systemic circulation and can theoretically treat the primary
tumor and any metastatic disease.
• Biologic therapies are currently considered in the broader sense
of immunotherapy or “targeted therapies.”
• Immunotherapy, the earliest important form of biologic
therapy, usually involves stimulating the host’s immune
system to fight the cancer.

29. • The agents used in immunotherapy are usually naturally occurring
cytokines, which have been produced with recombinant DNA
technology.
• Examples of agents used in immunotherapy include interferons
and interleukins (ILs).
• Targeted therapies include monoclonal antibodies, tyrosine
kinase inhibitors, proteosome inhibitors, and others.
• Many cancers appear to be eliminated by surgery or radiation.
However, the high incidence of later recurrence implies that the
primary tumor began to metastasize before it was removed.
• These early metastases are too small to detect with currently
available diagnostic tests and are known as micrometastases.
• Adjuvant therapy is defined as the use of systemic agents to
eradicate micrometastatic disease following localized modalities
such as surgery or radiation or both.

30. • The goal of systemic therapy given in this setting is to reduce
subsequent recurrence rates and prolong long-term survival.
• Thus, adjuvant therapy is given to patients with potentially
curable malignancies who have no clinically detectable
disease after surgery or radiation.
• Because adjuvant therapy is given at a time that the cancer
is undetectable (i.e., no measurable disease), its effectiveness
cannot be measured by response rates; instead, it is evaluated
by recurrence rates and survival.
• The value of adjuvant therapy is best established in
colorectal and breast cancers.
• Drug therapy may also be given in the neoadjuvant or
preoperative setting. The goals in this instance are to make
other treatment modalities more effective by reducing tumor
burden and to destroy micrometastases.

31. • For example, in head and neck cancer, neoadjuvant
chemotherapy is employed in an attempt to shrink large tumors
and to make them more amenable to later surgical resection, and
possibly spare critical organs, such as the larynx.
• The management of most types of cancer involves the use of
combined modalities.
• Early stage breast cancer is a good example of the use of a
combined-modality approach.
• The primary tumor is removed surgically, and radiation therapy
is delivered to the remaining breast (after lumpectomy) or to the
axilla (if there is marked lymph node involvement).
• Adjuvant therapy (chemotherapy, targeted therapy, and/or
hormonal therapy) is then administered to eradicate any
micrometastatic disease.

32. TREATMENT Principles of Drug Therapy
PURPOSES OF CHEMOTHERAPY
• The era of modern cancer chemotherapy was born in 1941,
when Goodman and Gilman first administered nitrogen
mustard to patients with lymphoma.
• Since then, numerous antineoplastic agents have been
developed, and a variety of chemotherapy regimens have been
investigated in every type of cancer.
• Table 130–7 lists tumors and their responsiveness to
chemotherapy.
• Cancer chemotherapy may be indicated as a primary,
palliative, adjuvant, or neo adjuvant treatment modality.

33. • Treatment with cytotoxic drugs is the primary curative
modality for a few diseases, including leukemias, lymphomas,
choriocarcinomas, and testicular cancer.
• Most solid tumors are not curable with chemotherapy alone,
either because of the biology of the tumor or because of
advanced disease at presentation.
• Chemotherapy in this setting is often initiated for palliative
purposes.
• It is often possible to decrease tumor size or to retard growth
enough to reduce untoward symptoms caused by the tumor.
• Adjuvant and neoadjuvant chemotherapy are defined in the
previous section

35. MOLECULAR AND CELLULAR BASIS FOR
DRUG THERAPY
PRINCIPLES OF TUMOR GROWTH
• The study of tumor growth forms the foundation for many of
the basic principles of modern cancer chemotherapy.
• The growth of most tumors is illustrated by the gompertzian
tumor growth curve (Fig. 130–4).
• Gompertz was an insurance actuary who described the
relationship between age and expected death.
• This mathematical model also approximates tumor cell
proliferation.
• In the early stages, tumor growth is exponential, which means
that the tumor takes a constant amount of time to double its
size. During this early phase, a large portion of the tumor cells
is actively dividing. This population of cells is called the
growth fraction.

36. • The doubling time, or time required for the tumor to double in
size, is very short.
• Because most anticancer drugs have greater effect on rapidly
dividing cells, tumors are most sensitive to the effects of
chemotherapy when the tumor is small and the growth fraction is
high.
• However, as the tumor grows, the doubling time is slowed.
• Wide variability exists in measured doubling times for different
cancers.
• The doubling time of most solid tumors is about 2 to 3 months.
However, some tumors have doubling times of only days (e.g.,
aggressive lymphomas) and others have even longer doubling
times (e.g., some salivary gland tumors)

37. • Figure 130–4 also illustrates the impact of tumor burden. It
takes about 109 cancer cells (1-g mass, 1 cm in diameter) for a
tumor to be clinically detectable by palpation or radiography.
• Such a tumor has undergone about 30 doublings in cell number.
• It only takes 10 additional doublings for this 1-g mass to reach 1
kg in size.
• A tumor possessing 1012 cancer cells (1-kg mass) is considered
lethal.
• Thus a tumor is clinically undetectable for most of its life span.
• Tumor burden also impacts response to chemotherapy. The cell
kill hypothesis states that a certain percentage of cancer cells
(not a certain number of cells) will be killed with each course of
chemotherapy. For example, if a tumor consists of 1,000 cancer
cells and the chemotherapy regimen kills 90% of the cells, then
10% or 100 cancer cells remain.

38. • The second chemotherapy course kills another 90% of cells,
and again only 10% or 10 cells remain.
• According to this hypothesis, the tumor burden will never
reach zero.
• Tumors consisting of less than 104 cells are believed to be
small enough for elimination by host factors, including
immunologic mechanisms, and these factors must be in place
for a cure to be possible.
• The limitations of this theory are that it assumes all cancers
are equally responsive and that drug resistance and metastases
do not occur.

40. TUMOR PROLIFERATION
• Both cancer cells and normal cells reproduce in a series of
steps known as the cell cycle.
• Figure 130–5 depicts the cell cycle and the phases of activity
for commonly used antineoplastic agents.
• The first phase is mitosis (M). Mitosis lasts for about 30 to
60 minutes and during this phase, cell division occurs.
• After mitosis, the cell might enter a dormant phase (G0), or
might proceed to the first gap phase (G1).
• G0 is the largest variable in the cell cycle, and during this
resting phase, the cell is not actively committed to cell
division.
• Some stimulus causes the cell to enter the first gap phase (G1).
During G1, the cell prepares for DNA synthesis by
manufacturing necessary enzymes.

41. • DNA synthesis (S) occurs next, and this phase lasts 10 to 20 hours.
• The percentage of cells in the S phase can be measured by flow
cytometry and is an indicator of the rate of tumor-cell proliferation.
• Tumors with a high percentage of S-phase cells are aggressively
growing.
• The synthesis phase is followed by a second gap or premitotic phase
(G2), lasting 2 to 10 hours.
• During this second gap, the cell prepares for mitosis by producing
ribonucleic acid (RNA) and specialized proteins, as well as the mitotic
spindle apparatus.
• The cycle then begins again with the M phase. Most normal human cells
exist in the G0 phase, and most cancer cells are not sensitive to the
effects of chemotherapy when they are in this stage.
• The cell cycle is regulated by external mitogens, including cytokines,
hormones, and growth factors. As mentioned earlier, some of the genes
that regulate the cell cycle are known to be protooncogenes and tumor
suppressor genes

42. • All cancer cells do not proliferate faster than normal cells; some
cancer cells reproduce more rapidly while others are more indolent.
• Many anticancer drugs target rapidly proliferating cells (both
normal and cancerous cells), and these agents may act at selective or
multiple sites of the cell cycle.
• Agents with major activity in a particular phase of the cell cycle are
known as cell-cycle phasespecific agents.
• The antimetabolites exert their major effect during the S phase.
Cell-cycle phase-specific agents may also be active to a lesser
extent in other phases of the cycle.
• Cell-cycle phase-nonspecific agents are those with significant
activity in multiple phases.
• The alkylating agents, such as nitrogen mustard, are examples. In
many cases, the cytotoxic effects of a drug may result from
interactions with other intracellular activities and are not related to
specific cellcycle events. Hormones are an example of this type of
drug.

43. • Knowledge of cell-cycle specificity has been applied to the
scheduling of chemotherapy administration.
• By definition, cell-cycle phase-specific agents exert their
major activity when cells are in a particular phase of the cell
cycle.
• At any given time, the heterogeneous cell populations within a
tumor are at various phases in the cell cycle.
• By giving phase-specific agents as a continuous infusion or in
multiple repeated fractions, clinicians can theoretically target
more cells as they progress into the drug-sensitive phase.
• Thus cellcycle phase-specific agents are also termed schedule
dependent.
• In contrast, cell-cycle phase-nonspecific drugs are active in
many phases, and consequently are not schedule dependent.
The activity of this group of drugs depends on the dose, and
these drugs are termed dose dependent.

45. MOLECULAR BIOLOGY
• Because many antineoplastic agents interfere with the cellular
synthesis of DNA, RNA, and proteins, it is important to review the
basic principles of molecular biology.
• Each normal human cell contains 46 chromosomes, which are
composed of DNA (deoxyribonucleic acid). DNA carries
hereditary information in units called genes.
• A single chromosome can contain 20,000 or more genes. Genes
code for specific proteins that regulate cellular activity and
inherited traits (some of which affect carcinogenesis and cancer
growth, as well as the efficacy and metabolism of anticancer
drugs).
• The genetic information is encoded in DNA by precise sequencing
of subunits known as nucleotides. Each nucleotide consists of a
sugar (deoxyribose), phosphoric acid, and a base. Four bases exist
in DNA: adenine, thymine, guanine, and cytosine.

46. • Adenine and guanine are purine-type bases; thymine and cytosine
are pyrimidine-type bases (Fig. 130–6).
• These nucleotides are connected linearly to form a chain. Each
DNA molecule is made up of two chains of nucleotides, which
wind around each other to form a double helix. The two strands
are held together by chemical bonding between the bases.
• The bonding process is very specific—adenine binds only with
thymine, and guanine binds only with cytosine. This is known as
complementary base pairing.
• RNA is important in the DNA-directed synthesis of proteins or
enzymes.
• RNA differs from DNA in that it is composed of a single strand
of nucleotides, the sugar is ribose, and the base uracil is
substituted for thymine. There are three known types of RNA:
messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal
RNA (rRNA).

48. DNA SYNTHESIS
• During the DNA synthesis phase, which takes place in the cell
nucleus, the DNA unwinds and exposes its nucleotides.
• When DNA unwinds for replication or protein synthesis, only
the portion of the molecule containing the needed nucleotides
needs to be exposed.
• Rather than unwinding the entire strand, topoisomerase I and
II enzymes cleave the DNA strands to facilitate unwinding of
the section that is needed.
• The enzyme DNA polymerase matches free complementary
nucleotides from the environment to the exposed nucleotides
of the DNA.
• The newly created strands rewind, resulting in two complete
double helices. The topoisomerase enzymes are also
responsible for resealing the cleaved DNA strands.

49. PROTEIN SYNTHESIS
• The synthesis of proteins is a more complex process. Proteins consist of
chains of amino acids in very specific sequences.
• As in DNA synthesis, the double helix must unwind. However, in
protein synthesis, only the portion of the DNA molecule that codes for
the desired protein is exposed.
• The enzyme RNA polymerase matches free complementary RNA
nucleotides to the exposed DNA nucleotides, and the resultant chain of
nucleotides is called mRNA.
• This process is called transcription. The mRNA travels to ribosomes in
the cytoplasm, where protein synthesis occurs.
• Each three nucleotides of the mRNA chain compose a codon, whose
sequence is specific for a particular amino acid.
• The codon is recognized by tRNA, which then carries the amino acid to
the ribosome, where it is added to the growing peptide chain. This
process is known as translation. The completed protein is then ready for
its intended use as an enzyme or as a structural component.