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Cancer & cancer drug
1. Cancer & Cancer Drug
Md. Shariful Islam
International Islamic University Chittagong
2. Neoplasm
ï” A new and abnormal growth of tissue in some part of the body, especially as a
characteristic of cancer.
ï” Neoplasm is an abnormal growth of tissue, and when also forming a mass is
commonly referred to as a tumor.
WHO classifies neoplasm into 4 groups-
1. Benign neoplasm
2. In-situ neoplasm
3. Malignant Neoplasm (Cancer)
4. Neoplasm of uncertain or Unknown behavior
3. Capecitabine
ï” Capecitabine is an anti-cancer ("antineoplastic" or "cytotoxic")
chemotherapy drug. Capecitabine is classified as an âantimetaboliteâ.
Capecitabine (INN) is an orally-administered chemotherapeutic agent
used in the treatment of numerous cancers. Capecitabine is a prodrug,
that is enzymatically converted to 5-fluorouracil (5-FU) in the body.
ï” It is on the World Health Organization's List of Essential Medicines, a
list of the most important medications needed in a basic health system.
4. Mechanism of Action
ï” Capecitabine is one of a group of chemotherapy drugs known as the anti
metabolites. These stop cells making and repairing DNA. Cancer cells need
to make and repair DNA in order to grow and multiply.
ï” Capecitabine is metabolised to 5-FU which in turn is a thymidylate synthase
inhibitor, hence inhibiting the synthesis of thymidine monophosphate
(ThMP), the active form of thymidine which is required for the de novo
synthesis of DNA
5. Mechanism Action With figure
Capecitabine or 5-FU acts in several ways, but principally as a thymidylate
synthase (TS) inhibitor. Interrupting the action of this enzyme blocks synthesis
of the pyrimidine thymidine, which is a nucleoside required for DNA
replication. Thymidylate synthase methylates deoxyuridine monophosphate
(dUMP) to form thymidine monophosphate (dTMP). Administration of 5-FU
causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell
death via thymineless death. Calcium folinate provides an exogenous source of
reduced folinates and hence stabilises the 5-FU-TS complex, hence enhancing
5-FU's cytotoxicity.
9. Adverse effects
âąAppetite loss
âąDiarrhea
âąVomiting
âąNausea
âąStomatitis
âąAbdominal pain
âąFatigue
âąWeakness
âąHand-foot syndrome
âąOedema
âąFever
âąPain
âąHeadache
âąHair loss
âąDermatitis
Contraindications
âąHistory of hypersensitivity to fluorouacil, capecitabine or
any of its excipients.
âąPatients with DPD (dihydropyrimidine dehydrogenase)
deficiency
âąPregnancy and lactation
âąPatients with pre-existing blood dyscrasias.
âąPatients with severe hepatic impairment or severe renal
impairment
âąTreatment with sorivudine or its chemically related
analogues, such as brivudine
11. ContinueâŠâŠ
ï” Route of elimination:
Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of
administered capecitabine dose is recovered in urine. Fecal excretion is minimal
(2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the
administered dose. About 3% of the administered dose is excreted in urine as
unchanged drug.
Half life
45-60 minutes for capecitabine and its
metabolites.
12. Doses
How Capecitabine Is Given:
ï” Taken as a pill by mouth.
ï” Take after food (within 30 minutes of a meal) with water. (Usually taken in a divided
dose 12 hours apart).
ï” Tablets come in 2 sizes; 150mg and 500mg.
ï” Do not crush, chew or dissolve tablets.
ï” The amount of Capecitabine that you will receive depends on many factors, including
your height and weight, your general health or other health problems, and the type of
cancer or condition being treated. Your doctor will determine your dose and
schedule.
13. International and National Market
Preparation
1. Xeloda (500mg)
Company: Roche Bangladesh limited
2. Xitabin (500 mg)
Company : Beacon Pharmaceuticals Limited
3. Captabine (150mg & 500mg)
Company : Techno Drugs Ltd.
4. Xeloda (150 mg & 500 mg)
Company: F. Hoffmann La Roche, Switzerland
14. 5-Fluorouracil (2,4-Dioxo-5-fluoropyrimidine)
ï” 5-FU is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy
drug. It is a drug that is a pyrimidine analog which is used in the treatment of
cancer. It is a suicide inhibitor and works through irreversible inhibition of
thymidylate synthase. It belongs to the family of drugs called the
antimetabolites.
ï” Fluorouracil is also known as FU or 5FU and is one of the most commonly
used drugs to treat cancer. It is used to treat many types of cancer including,
breast cancer, head and neck cancers, anal cancer, stomach cancer,
colon cancer and some skin cancers.
It may be combined with other cancer drugs or with radiotherapy.
It has also been given topically for actinic keratoses and Bowen's disease
15. History
ï” In 1954 Abraham Cantarow and Karl Paschkis found liver tumors absorbed
radioactive uracil more readily than normal liver cells. Charles Heidelberger,
who had earlier found that fluorine in fluoroacetic acid inhibited a vital
enzyme, asked Robert Duschinsky and Robert Schnitzer at Hoffman-La
Roche to synthesize fluorouracil.
16. Mechanism of Action
ï” 5-FU acts in several ways, but principally as a thymidylate synthase (TS)
inhibitor. Interrupting the action of this enzyme blocks synthesis of the
pyrimidine thymidine, which is a nucleoside required for DNA replication.
Thymidylate synthase methylates deoxyuridine monophosphate (dUMP) to
form thymidine monophosphate (dTMP). Administration of 5-FU causes a
scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via
thymineless death. Calcium folinate provides an exogenous source of
reduced folinates and hence stabilises the 5-FU-TS complex, hence
enhancing 5-FU's cytotoxicity.
20. Contraindications
ï” It is contraindicated in patients that are severely debilitated or in patients
with myelosuppression due to either radiotherapy or chemotherapy. It is
likewise contraindicated in pregnant or breastfeeding women. It should also
be avoided in patients that do not have malignant illnesses.
22. Carboplatin
ï” Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy
drug. Carboplatin is classified as an âalkylating agentâ.
ï” Carboplatin, or cis-diammine (1,1-cyclobutanedicarboxylato)platinum(II) (trade
names Paraplatin and Paraplatin-AQ) is a chemotherapy drug used against some forms
of cancer(mainly ovarian carcinoma, lung, head and neck cancers as well as
endometrial, esophageal, bladder, breast and cervical; central nervous system or
germ cell tumors; osteogenic sarcoma, and as preparation for a stem cell or bone
marrow transplant). It was introduced in the late 1980s and has since gained popularity
in clinical treatment due to its vastly reduced side effects compared to its parent
compound cisplatin. Cisplatin and carboplatin belong to the group of platinum-based
antineoplastic agents, and interact with DNA to interfere with DNA repair.
23. History
ï” Carboplatin was discovered at Michigan State University and developed at the Institute of
Cancer Research in London. Bristol-Myers Squibb gained Food and Drug Administration
(FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989.
Starting in October 2004, generic versions of the drug became available.
ï” Pharmacodynamics:
Carboplatin is an antineoplastic in the class of alkylating agents and is used to treat various
forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to
many electronegative groups under conditions present in cells. They stop tumor growth by cross-
linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the
strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no
longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where
they do not belong which in turn inhibits their correct utilization by base pairing and causes a
miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three
different mechanisms all of which achieve the same end result - disruption of DNA function and
cell death.
24. Mechanism of Action
ï” Alkylating agents work by three different mechanisms:
1) Attachment of alkyl groups to DNA bases, resulting in the DNA being
fragmented by repair enzymes in their attempts to replace the alkylated bases,
preventing DNA synthesis and RNA transcription from the affected DNA,
2) DNA damage via the formation of cross-links (bonds between atoms in the
DNA) which prevents DNA from being separated for synthesis or transcription,
and
3) the induction of mispairing of the nucleotides leading to mutations.
25. Carboplatin Side Effects:
ï” The following side effects are common (occurring in greater than 30%) for patients
taking Carboplatin:
Low blood counts (including red blood cells, white blood cells and platelets)
ï The main drawback of carboplatin is its myelosuppressive effect. This
causes the blood cell and platelet output of bone marrow in the body to
decrease quite dramatically, sometimes as low as 10% of its usual production
levels. This myelosuppression usually occurs 21â28 days after the first
treatment, after which the blood cell and platelet levels in the blood begin to
stabilize, often coming close to its pre-carboplatin levels. This decrease in
white blood cells (neutropenia) can cause complications, and is sometimes
treated with drugs like filgrastim.
26. Other Side effects
âąNausea and vomiting
âąDiarrhea
âąMouth ulcers and loss of appetite
âąBone marrow suppression leading to anemia
âąKidney and liver function may be affected.
âąHearing loss may be seen, especially in children receiving carboplatin.
âą There may be short-term vision loss.
âąHearing loss, especially in children receiving the therapy.
âąHair loss (this is usually regained after completion of therapy).
âąRarely, allergic reactions occur such as skin rashes, itching
27. Pharmacokinetic
ï” After a 1 hour infusion of carboplatin, the blood levels of total platinum and free
platinum reduce in a biphasic manner. For the free platinum, the first phase of the
half life (when the drug achieves half its plasma concentration) is around 90
minutes. In the later phase, the half life is around 6 hours. All free platinum is in
the form of carboplatin for the first four hours.
ï” Once administered, the drug binds to plasma proteins. Protein binding is less than
with cisplatin. Initially, protein binding is low, with around 29% of the
carboplatin bound in the first 4 hours. However, within 24 hours, 85-89% of the
platinum in the drug is bound irreversibly to the plasma proteins and is gradually
eliminated with a minimum half life of five days.
ï” Carboplatin is excreted via the kidneys. Most of the excretion occurs within
the first 6 hours after the drug is administered and around 50% to 60% is excreted
within 24 hours. Of all the medication administered, 32% is excreted unchanged
in urine.
28. How Carboplatin Is Given:
ï” Carboplatin is usually given by infusion into a vein (intravenous, IV).
ï” Carboplatin can also be given intra-peritoneal, directly into the peritoneal
cavity in the abdomen.
ï” The amount of Carboplatin you receive depends on many factors, including
your height and weight, your general health or other health problems, and
how your body responds to it. Your doctor will determine your dose and
schedule.
30. Latest Information
ï” A recent study in mutant mice suggests that in the subset of women with breast
cancer due to BRCA1 and BRCA2 genes (these cause a variety of familial breast
cancer) carboplatin may be as much as 20 times more effective than the usual
breast cancer treatments.
ï” Carboplatin has also been used to treat testicular cancer patients with stage 1
seminoma. Recent research indicates that this treatment is more effective and has
fewer side effects than adjuvant radiotherapy
ï” Carboplatin should not be used to treat patients with the following conditions:
Severe kidney disease
Allergy to carboplatin
Severe bone marrow depression
Severe bleeding
Pregnant and breastfeeding women
31. Cisplatin (Penicillin of Cancer)
ï” Cisplatin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Cisplatin is classified as an
"alkylating agent."
ï” Cisplatin, cisplatinum, platamin, neoplatin, cismaplat or cis-diamminedichloroplatinum(II)(CDDP) is
a chemotherapy drug. It was the first member of a class of platinum-containing anti-cancer drugs, which
now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and
causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death).
ï” .
32. History
ï” Cisplatin is a chemotherapy drug which is used to treat cancers including: sarcoma, small cell
lung cancer, germ cell tumors, lymphoma, and ovarian cancer. While it is often considered an
alkylating agent, it contains no alkyls groups and does not instigate alkylating reactions, so it is
properly designated as an alkylating-like drug. Cisplatin is platinum-based and was the first
medicine developed in that drug class. Other drugs in this class include carboplatin, a drug with
fewer and less severe side effects introduced in the 1980s, and oxaliplatin, a drug which is part
of the FOLFOX treatment for colorectal cancer. The other names for cisplatin are DDP,
cisplatinum, and cis-diamminedichloridoplatinum(II) (CDDP). Cisplatin was actually first
created in the mid 19th Century and is also known as Peyrone's chloride. (The discoverer was
Michel Peyrone.) It wasn't until the 1960s that scientists started getting interested in its
biological effects, and cisplatin went into clinical trials for cancer therapy in 1971. By the late
1970s it was already widely used and is still used today despite the many newer chemotherapy
drugs developed over the past decades
33. Why it is called penicillin of Cancer
ï” Cisplatin is called the âpenicillin of cancerâ because it is used so widely and
it was the first big chemotherapy drug. Cisplatin also plays an interesting role
in the history of chemistry. First synthesized in the 1800s, long before
anyone thought of using it against cancer, cisplatin is a target compound
chemists use to prove their moxie in inorganic synthesis. The shape and
symbols of the molecule as represented in that discipline's iconography is
aesthetically pleasing which is another reason people like to talk about
cisplatin.
34. Indication
ï” Used to treat testicular, ovarian, bladder, head and neck, esophageal, small and non-small
cell lung, breast, cervical, stomach and prostate cancers. Also to treat Hodgkin's and non-
Hodgkin's lymphomas, neuroblastoma, sarcomas, multiple myeloma, melanoma, and
mesothelioma.
ï” Side Effect:
ï” Nausea and vomiting (Nausea may last up to 1 week after therapy. Anti-nausea medication is
given before the infusion, and a prescription is also given for use after. )
ï” Kidney toxicity (Effects on kidney function are dose related, observed 10-20 days after therapy,
and are generally reversible)
ï” Blood test abnormalities(low magnesium, low calcium, low potassium)
ï” Low white blood cells(this may put you at increased risk for infection)
ï” Low red blood cells(anemia)
37. How this drug is given:
âąCisplatin is administered through a vein (intravenously or IV) as an infusion.
âąThere is no pill form of Cisplatin.
âąCisplatin is an irritant. An irritant is a chemical that can cause inflammation of the vein through which it is given.
âąIf Cisplatin escapes from the vein it can cause tissue damage.
So, The nurse or doctor who gives Cisplatin must be carefully trained.
âąBefore and/or after the Cisplatin infusion, extra IV fluids are given, care is taken to ensure adequate hydration before,
during and after Cisplatin, to protect your kidney function.
âąCisplatin also has been used as an infusion into the abdominal cavity (contains the abdominal organs).
âąThe amount of Cisplatin that you receive depends on many factors, including your height and weight
38. Cyclophosphamide
ï” Cyclophosphamide is an anti-cancer (âantineoplasticâ or âcytotoxicâ) chemotherapy drug. This
medication is classified as an alkylating agent.
ï” Cyclophosphamide (INN, trade names Endoxan, Cytoxan, Neosar, Procytox, Revimmune,
Cycloblastin), also known as cytophosphane and CP, is a nitrogen mustard alkylating agent from
the oxazaphosphorine group.
ï” An alkylating agent adds an alkyl group to DNA. It attaches the alkyl group to the guanine base of
DNA, at the number 7 nitrogen atom of the imidazole ring. This interferes with DNA replication by
forming intrastrand and interstrand DNA crosslinks.
ï” Cyclophosphamide is used to treat cancers, autoimmune disorders, and AL amyloidosis. As a
prodrug, it is converted by liver cytochrome P450 (CYP) enzymes to form the metabolite 4-hydroxy
cyclophosphamide that has chemotherapeutic activity.
ï” Cyclophosphamide has severe and life-threatening adverse effects, including acute myeloid
leukemia, bladder cancer, hemorrhagic cystitis, and permanent infertility, especially at higher doses.
For autoimmune diseases, doctors often substitute less-toxic methotrexate or azathioprine after an
acute crisis.
39. History
As reported by O.M. Colvin in his study of the development of cyclophosphamide and its clinical applications,
Phosphoramide mustard, one of the principle toxic metabolites of cyclophosphamide,
was synthesized and reported by Friedman and Seligman in 1954.
It was postulated that the presence of the phosphate bond to the nitrogen atom could inactivate the nitrogen
mustard moiety, but the phosphate bond would be cleaved in gastric cancers and other tumors which had a
high phosphamidase content.
41. Side effects:
ï” nausea
ï” vomiting
ï” loss of appetite or weight
ï” abdominal pain
ï” diarrhea
ï” hair loss
ï” sores on the mouth or tongue
ï” changes in skin color
ï” changes in color or growth of finger or toe nails
43. Oxaliplatin
Oxaliplatin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy
drug. Oxaliplatin is classified as an "alkylating agent.
Oxaliplatin, marketed as Eloxatin by Sanofi, is a platinum-based antineoplastic agent
used in cancer chemotherapy.
Oxaliplatin is used to treat colon or rectal cancer that has spread (metastasized), it is
often given in combination with other anticancer drugs (fluorouracil and leucovorin).
44. Mechanism of Action
ï” The compound features a square planar platinum(II) center. In contrast to
cisplatin and carboplatin, oxaliplatin features the bidentate ligand 1,2-
diaminocyclohexane in place of the two monodentate ammine ligands. It also
features a bidentate oxalate group.
ï” According to in vivo studies, oxaliplatin fights carcinoma of the colon
through non-targeted cytotoxic effects. Like other platinum compounds, its
cytotoxicity is thought to result from inhibition of DNA synthesis in cells. In
particular, oxaliplatin forms both inter- and intra-strand cross links in DNA,
which prevent DNA replication and transcription, causing cell death.
45. Adverse effects
ï” Neurotoxicity
ï” Nausea, vomiting, or diarrhea
ï” Fatigue
ï” Neutropenia (low number of a type of white blood cells
ï” Ototoxicity (hearing loss)
ï” Extravasation if oxaliplatin leaks from the infusion vein it may cause severe
damage to the connective tissues.
ï” Hypokalemia (low blood potassium), which is more common in women than
men
47. How Oxaliplatin Is Given:
âąIt is given by infusion into the vein (intravenous, IV).
âąThere is no pill form of Oxaliplatin.
48. Docetaxel
Docetaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is
classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent
Docetaxel (as generic or under the trade name Taxotere or Docecad) is a clinically well-established anti-
mitotic chemotherapy medication that works by interfering with cell division. Docetaxel is approved by
the FDA for treatment of locally advanced or metastatic breast cancer, head and neck cancer, gastric
cancer, hormone-refractory prostate cancer and non small-cell lung cancer. Docetaxel can be used as a
single agent or in combination with other chemotherapeutic drugs as indicated depending on specific
cancer type and stage.
Docetaxel is a member of the taxane drug class, which also includes the chemotherapeutic medication
paclitaxel. Although docetaxel remains twice as potent as paclitaxel (due to docetaxelâs effect on the
centrosome of the mitotic spindle), the two taxanes have been observed to have comparable efficacy.
Several recent articles have found "no evidence that regimens containing docetaxel yield greater benefits
than those including paclitaxel." While efficacy between the two agents has been observed to be
equivalent, paclitaxel may cause fewer side effects. Additionally, it has been noted that docetaxel is prone
to cellular drug resistance via a variety of different mechanisms
49. Medical uses
ï” Approved in treatment of breast cancer, non-small cell lung cancer, advanced
stomach cancer, head and neck cancer and metastatic prostate cancer.
ï” Also being investigated to treat small cell lung, ovarian, bladder, and
pancreatic cancers, soft tissue sarcoma and melanoma.
50. Modes of action
ï” The cytotoxic activity of docetaxel is exerted by promoting and stabilising microtubule
assembly, while preventing physiological microtubule depolymerisation/disassembly in
the absence of GTP. This leads to a significant decrease in free tubulin, needed for
microtubule formation and results in inhibition of mitotic cell division between metaphase
and anaphase, preventing further cancer cell progeny.
ï” Because microtubules do not disassemble in the presence of docetaxel, they accumulate
inside the cell and cause initiation of apoptosis. Apoptosis is also encouraged by the
blocking of apoptosis-blocking bcl-2 oncoprotein. Both in vitro and in vivo analysis show
the anti-neoplastic activity of docetaxel to be effective against a wide range of known
cancer cells, cooperate with other anti-neoplastic agents activity, and have greater
cytotoxicity than paclitaxel, possibly due to its more rapid intracellular uptake.
ï” The main mode of therapeutic action of docetaxel is the suppression of microtubule
dynamic assembly and disassembly, rather than microtubule bundling leading to
apoptosis, or the blocking of bcl-2
51. Adverse effects
ï” Docetaxel is a chemotherapeutic agent and is a cytotoxic compound and so is
effectively a biologically damaging drug.As with all chemotherapy, adverse effects
are common and many varying side-effects have been documented. Because
docetaxel is a cell cycle specific agent, it is cytotoxic to all dividing cells in the body.
This includes tumour cells as well as hair follicles, bone marrow and other germ cells.
For this reason, common chemotherapy side effects such as hair loss occur;
sometimes this can be permanent. North west France are conducting a survey to
establish exactly how many people are being affected in this way. Independent studies
show it could be as high as 6.3% which puts this it in the 'common and frequent'
classification
ï” Haematological adverse effects include Neutropenia (95.5%), Anaemia (90.4%),
Febrile neutropenia (11.0%) and Thrombocytopenia (8.0%). Deaths due to toxicity
accounted for 1.7% of the 2045 patients and incidence was increased (9.8%) in
patients with elevated baseline liver function tests (liver dysfunction
54. How this drug is given:
âąDocetaxel is given through a vein (intravenously, IV)
âąThere is no pill form of docetaxel
55. Doxorubicin
Doxorubicin is an anti-cancer (âantineoplasticâ or âcytotoxicâ) chemotherapy
drug. Doxorubicin is classified as an âanthracycline antiobiotic
Cancers treated with Doxorubicin include: bladder, breast, head and neck, leukemia (some
types), liver, lung, lymphomas, mesothelioma, multiple myeloma, neuroblastoma, ovary,
pancreas, prostate, sarcomas, stomach, testis (germ cell), thyroid, uterus.
Doxorubicin (INN) trade name Adriamycin; pegylated liposomal form trade name Doxil or
Caelyx; nonpegylated liposomal form trade name Myocet), also known as
hydroxydaunorubicin and hydroxydaunomycin, is a drug used in cancer chemotherapy and
derived by chemical semisynthesis from a bacterial species. It is an anthracycline antitumor
antibiotic closely related to the natural product daunomycin and like all anthracyclines, it
works by intercalating DNA, with the most serious adverse effect being life-threatening heart
damage. It is commonly used in the treatment of a wide range of cancers, including
hematological malignancies (blood cancers, like leukaemia and lymphoma), many types of
carcinoma (solid tumours) and soft tissue sarcomas. It is often used in combination
chemotherapy as a component of various chemotherapy regimens.
56. Adverse Effect
ï” Common adverse effects of doxorubicin include hair loss (seen in most of those
treated with the drug), myelosuppression (a compromised ability of the body's
bone marrow to produce new blood cells), nausea and vomiting (which are seen
in roughly 30-90% of people treated with the drug), oral mucositis, oesophagitis,
diarrhoea, skin reactions (including hand-foot syndrome) and localised swelling
and redness along the vein in which the drug is delivered. Less common, yet
serious reactions include hypersensitivity reactions (including anaphylaxis),
radiation recall, heart damage and liver dysfunction
ï” Route: The drug is administered intravenously, as the hydrochloride salt.
57. Mechanism of Action
ï” Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular
biosynthesis. This inhibits the progression of the enzyme topoisomerase II, which relaxes
supercoils in DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex
after it has broken the DNA chain for replication, preventing the DNA double helix from
being resealed and thereby stopping the process of replication. It may also increase free
radical production, hence contributing to its cytotoxicity.
ï” The planar aromatic chromophore portion of the molecule intercalates between two base
pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove
and interacts with flanking base pairs immediately adjacent to the intercalation site, as
evidenced by several crystal structures.
ï” By intercalation, doxorubicin can also induce histone eviction from chromatin. As a result,
DNA damage response, epigenome and transcriptome are deregulated in doxorubicin-
exposed cells