Anti Cancer Drugs

Dr Shabzain Ishrat
ANTI CANCER DRUGS

Introduction
 Cancer is a disease characterized by
uncontrolled multiplication and
spread of abnormal forms of the body's own
cells
 A normal cell turns into a cancer cell

because of
one or more mutations in its DNA, which can
be acquired or inherited
 Cancer arises as a result of a series of
Genetic and
Epigenetic changes
 The main genetic lesions being:

Inactivation of tumor suppressor genes
Activation of oncogenes (mutation of the
normal genes controlling cell division and
other processes).
 Cancer cells characteristics that
distinguish them from normal cells;
Uncontrolled proliferation
Dedifferentiation and loss of function
Invasiveness
Metastasis
Cell cycle
Cell compartments of solid tumors
 Compartment A consists of dividing cells,
possibly being continuously in cell cycle
 Compartment B consists of resting cells

(G0 phase) which, although not dividing, are
potentially able to do so
 Compartment C consists of cells that are

no longer able to divide but which contribute
to the tumour volume
 Only cells in compartment A, which may
form as little as 5% of some solid tumors,
are susceptible to the main current cytotoxic
drugs which affect only one characteristic
aspect of cancer cell biology- cell division
 In many cases, the antiproliferative action is

during S phase of the cell cycle, and the
resultant damage to DNA initiates apoptosis
Classification of anticancer drugs
 Cell cycle–specific (CCS) drugs:
Acts on proliferating cells
Most effective in hematologic malignancies and
in solid tumors
○ in which a relatively large proportion of the cells
are proliferating
 Cell cycle–nonspecific (CCNS) drugs:

Can kill both G0 and cycling cells (although
cycling cells are more sensitive)
Used in slow growing tumors
Cell cycle specific (CCS) drugs
Antimetabolites (S phase)
• Cepecitabine
• Cladribine
• Cytarabine
• Clofarabine
• Fludarabine
• Fluorouracil
• Gemcitabine
• 6 mercaptopurine
• Methotrexate
• Nelarabine
• Pralatrexate
• 6 thioguanine
Topoisomerase II inhibitors (G1-S phase)
• Etoposide
Topoisomerase I inhibitors (G2-M)

• Topotecan
• Irinotecan
Antitumor antibiotics (G2–M phase)

• Bleomycin
Taxanes (M phase)
• Paclitaxel
• Cabazitaxel
• Docetaxel
Vinca alkaloids (M phase)

• Vinblastine
• Vincristine
• Vinorelbine
Antimicrotubule inhibitor (M phase)

• Ixabepilone
• Eribulin
Cell cycle nonspecific (CCNS) drugs
Alkylating agents
• Altretamine
• Bendamustine
• Busulfan
• Carmustine
• Chlorambucil
• Cyclophosphamide
• Dacarbazine
• Lomustine
• Mechlorethamine
• Melphalan
• Temozolomide’
• Thiotepa
Platinum analogs
• Carboplatin
• Cisplatin
• Oxaliplatin
Anthracyclines
• Daunorubicin
• Doxorubicin
• Epirubicin
• Idarubicin
• Mitoxantrone
Anti tumor antibiotics
• Dactinomycin
• Mitomycin
ANTIMETABOLITES
Antimetabolites
 These block or subvert one or more of
the metabolic pathways involved in DNA
synthesis
Antifolates antimetabloites
 Methotrexate
 Pemetrexed
 Pralatrexate
Methotrexate
 Folate analog
 Folates are essential for the synthesis of

purine nucleotides and thymidylate,
○ which in turn are essential for DNA synthesis
and cell division
 Methotrexate inhibits dihydrofolate

reductase
 Dihydrofolate reductase converts the
folate substrate (polyglutamates)
○ first to dihydrofolate (FH2),
○ then to FH4
 FH4 functions as an essential cofactor

carrying
The methyl groups necessary for the
Transformation of 2´-deoxyuridylate (DUMP) to the 2
´-deoxythymidylate/deoxythymidine monophosphate
(DTMP)
○ required for the synthesis of purines and DNA
Clinical uses
 Breast cancer
 Head and neck cancer
 Osteogenic sarcoma
 Primary central nervous system
lymphoma
 Non- Hodgkin’s lymphoma
 Bladder cancer
 Choriocarcinoma
Adverse effects of Methotrexate
 Mucositis
 Diarrhea
 Myelosuppression
 Neutropenia
 Thrombocytopenia
Pemetrexed
 Pyrrolopyrimidine antifolate analog
 Activity in the S phase of the cell cycle
 Inhibits
TS,
DHFR, and
purine nucleotide synthesis
Clinical uses
 Mesothelioma
 Non-small cell lung cancer
Adverse effects
 Skin rash
 Mucositis
 Diarrhea
 Fatigue
 Hand-foot syndrome
PURINE ANTAGONISTS
ANTIMETABOLITES
 Drugs
 6-mercaptopurine
 Fludarabine
 6 Mercaptopurine
 Inhibits several enzymes for purine biosynthesis
 Also forms metabolites like 6- methylmercaptopurine

ribotide (MMPR) which contribute to its cytotoxic action
 Fludarabine in its trisphosphate form inhibits DNA

polymerase
Clinical uses
AML
 Fludarabine
Non-Hodgkin Lymphoma
CLL
Adverse effects
Myelosuppression,
Immunosuppression,
Hepatotoxicity
 Fludarabine
Myelosuppression
Immunosuppression
Nausea and vomiting
Fever, myalgias, arthralgias
 6 mercaptupurine
 Inhibits de novo purine nucleotide
synthesis
 Inhbits incorporation of triphosphate into
RNA;
 Inhibits incorporation of triphosphate into
DNA
Clinical uses
 AML
ADVERSE EFFECTS
 Immunosuppression
 Hepatotoxicity
 6 thioguanine
 MOA, Clinical uses and adverse effects
Same as 6 mercaptopurine
PYRIMIDINE ANTAGONISTS
ANTIMETABOLITES
 Drugs
5-fluorouracil
Cytarabine
 5 Flurouracil
inhibit thymidylate synthetase hence
○ Inhibiting thymidilate synthesis
 Cytarabine
Inhibits DNA polymerase
Clinical uses
 Cytarabine
 AML
 ALL
 CML
 5 Flurouracil
 Colorectal cancer
 Anal cancer
 Breast cancer
 Gastroesophageal cancer
 Head and neck cancer
 Hepatocellular cancer
Adverse effects
 5 Flurouracil
 Nausea
 Mucositis
 Diarrhea
 Bone marrow depression
 Neurotoxicity
 Cytarabine
 Nausea and vomiting
 Myelosuppression with neutropenia and
thrombocytopenia
 Cerebellar ataxia
 Cepecitabine
 Inactive in its parent form
 Undergoes extensive metabolism in the liver
 By the enzyme carboxyl esterase
○ To an intermediate, 5′-deoxy-5-fluorocytidine
 This metabolite is then converted to 5′-deoxy-5-fluorouridine by

the enzyme cytidine deaminase
 Inhibits
 Thymidylate Synthase;
 Incorporation of 5-fluorouridine-5′-triphosphate (FUTP) into RNA
○ Resulting in alteration in RNA processing;
 Incorporation of 5-fluorodeoxyuridine-5′-triphosphate (FdUTP) into DNA
○ Resulting in inhibition of DNA synthesis and function
Clinical uses
 Breast cancer
 Colorectal cancer
 Gastroesophageal cancer
 Hepatocellular cancer
 Pancreatic cancer
Adverse effects
 Diarrhea
 Hand-foot syndrome
 Nausea and vomiting
 Gemcitabine
 Inhibits DNA synthesis and repair;
 Inhibits ribonucleotide reductase with

reduced formation of dNTPs;
 Incorporation of gemcitabine triphosphate

into DNA
Resulting in inhibition of DNA synthesis and
function
Clinical uses
 Bladder cancer
 Breast cancer
 ovarian cancer
 Non-hodgkin’s lymphoma
 Soft tissue sarcoma
Adverse effects
 Nausea, vomiting
 Diarrhea
ALKYLATING
AGENTS
Alkylating agents
 Contain chemical groups that can form crossbridge
covalent bonds with
 DNA
 Nucleophilic substances in the cell
 Form a carbonium ion-a cation, which is highly reactive

 React instantaneously with an electron donor (nucleophile) such
as:
○ Amine,
○ Hydroxyl or
○ Sulfhydryl group
 Cyclophosphamide is one of the most widely used

alkylating agents
 Major site of alkylation within DNA is the
N7 position of guanine
 To a lesser degree
N1 and N3 of adenine
N3 of cytosine
O6 of guanine
Phosphate atoms and proteins associated
with DNA
Adverse effects of alkylating agents
 Dose-related
 Occur primarily in rapidly growing tissues such as

 bone marrow (myelosuppression),
 gastrointestinal tract (diarrhea),
 reproductive system
 Potent vesicants and can damage tissues at the site of

administration
 carcinogenic in nature,
 Increased risk of secondary malignancies, especially acute
myelogenous leukemia
 Mechlorethamine
 CLINICAL USES
 Hodgkin’s and non-Hodgkin’s lymphoma
 ACUTE ADVERSE EFFECTS

 Chlorambucil
 MOA same as Mechlorethamine
 CLINICAL USES
 CLL and non-Hodgkin’s lymphoma

 Cyclophosphamide
 CLINICAL USES
 Breast cancer
 Ovarian cancer
 Non-hodgkin’s lymphoma
 CLL
 Neuroblastoma
 Wilms’ tumor
 Rhabdomyosarcoma

 Melphalan
 CLINCIAL USES
 Multiple myeloma
 Breast cancer
 Ovarian cancer
 ACUTE ADVERSE EFFECRS

 Thiotepa
 Clinical uses
 Breast cancer
 Ovarian cancer
 Superficial bladder cancer

 Busulfan
 CLINICAL USES
 CML

Delayed toxicity
 Mechlorethamine, Chlorambucil, Cyclophosphamide,
Bendamustine, Melphalan, Thiotepa, Busulfan
 These drugs cause

 Moderate depression of peripheral blood count;
 Excessive doses produce severe bone marrow depression with leukopenia,
thrombocytopenia, and bleeding
 Alopecia and hemorrhagic cystitis occasionally occur with

cyclophosphamide;
 Cystitis can be prevented with adequate hydration;
 Busulfan is associated with

 Skin pigmentation,
 Pulmonary fibrosis, and
 Adrenal insufficiency
Nitrousureas alkylating agents
 Carmustine
 Lomustine
 Lipid soluble
 Cross blood brain barrier
 Effective in brain tumors
 Carmustine
 Nitrosourea alkylating agent
 CLINICAL USES
 Brain cancer

 Lomustine
 Nitrosourea alkylating agent
 CLINCIAL USES
 Brain cancer

Delayed toxicity
 Carmustine and Lomustine
 Rarely interstitial lung disease
 Interstitial nephritis
 Altretamine
 CLINCIAL USES
 Ovarian cancer
 Acute Adverse effects

 Delayed adverse effects

 Myelosuppression,
 Peripheral neuropathy,
 Flu-like syndrome
 Temozolomide
 CLINCIAL USES
 Brain cancer
 Melanoma

 Headache and fatigue
 DELAYED ADVERSE EFFECTS

 Mild elevation in liver function tests
 Photosensitivity
Non classic alkylating agents
 Procarbazine
 Dacarbazine
 Bendamustine
 Procarbazine
 Non classic alkylating agent
 Clinical uses
 Hodgkin’s and non-Hodgkin’ lymphoma,
 Brain tumors
 Acute adverse effects

 Central nervous system depression

 Hypersensitivity reactions
 Dacarbazine
 CLINCIAL USES
 Hodgkin’s lymphoma,
 Melanoma,


 Myelosuppression,
 Central nervous system toxicity with
 Neuropathy
 Ataxia
 Lethargy
 Confusion
 Bendamustine
 CLINCIAL USES
 CLL
 Non-Hodgkin’s lymphoma

Platinum analogs
 Cisplatin
 Carboplatin
 Oxaliplatin
 Cisplatin
 CLINCIAL USES
 Non-small cell and small cell lung cancer,
 Breast cancer
 Bladder cancer
 Cholangiocarcinoma
 Ovarian cancer
 Germ cell cancer

 Nephrotoxicity
 Peripheral sensory neuropathy
 Ototoxicity
 Nerve dysfunction
 Carboplatin
 Clinical uses
 Non-small cell and small cell lung cancer
 Breast cancer
 Bladder cancer
 Ovarian cancer

 Rarely peripheral neuropathy
 Renal toxicity
 Hepatic dysfunction
 Oxaliplatin
 Clinical uses

 Laryngopharyngeal dysesthesias
 Diarrhea
NATURAL PRODUCT
ANTICANCER DRUGS
Natural product Anticancer drugs
 Vinca alkaloids
 Vinblastine
 Vincristine
 Vinorelbine
 Taxanes and other mictrotubule synthesis

inhibitors
 Paclitaxel
 Abraxane
 Docetaxel
 Cabazitaxel
 Ixabepilone
 Eribulin
 Epipodophyllotoxins
Etoposide
 Camptothecins
Topotecan
Irinotecan
Mechanism of action
 Inhibit the process of tubulin polymerization
 Disrupts assembly of microtubules,

especially those involved in the mitotic
spindle apparatus
 Work in the M phase of the cell cycle
 Cell division arrests in metaphase and cell

death occurs
Vinblastine
 Clinical uses
 Breast cancer
 Kaposi’s sarcoma
 Early Adverse effects

Myelosuppression
Mucositis
Alopecia
Syndrome of inappropriate secretion of
antidiuretic hormone (SIADH)
Vascular events
Vincristine
 Clinical uses
 ALL
 Rhabdomyosarcoma
 Neuroblastoma
 Wilms’ tumor
 Adverse effects
 Neurotoxicity with peripheral neuropathy
 Paralytic ileus
 Alopecia
 SIADH
Vinorelbine
 Clinical uses
 Breast cancer
 Ovarian cancer
 Adverse effects
 Constipation
 SIADH
TAXANES AND OTHER
MICROTUBULE
SYNTHESIS INHIBITORS
Mechanism of action
 Bind on microtubules, stabilising them in
the polymerized state
 Achieving a similar effect to that of the

vinca alkaloids by arresting mitosis
Paclitaxel
 Clinical uses
 Breast cancer
 Ovarian cancer
 Prostate cancer
 Bladder cancer
 Adverse effects
 Hypotension
 Arrhythmias
 Hypersensitivity
Abraxane
 Albumin-bound paclitaxel nanoparticle
formulation
 Clinical uses same as that of Paclitaxel
 Differs from paclitaxel by:

Not associated with hypersensitivity
reactions
Reduced incidence of myelosuppresion
Neurtoxicity is reversible
Docetaxel
 Semisynthetic taxane
 Clinical uses
 Breast cancer
 Prostate cancer
 Gastric cancer
 Ovarian cancer
 Bladder cancer
 Adverse effects
 Hypersensitivity
 Neurotoxicity
 Fluid retention
 Myelosuppression with neutropenia
Cabazitaxel
 Semisynthetic taxane
 Useful for treating multidrug-resistant

tumors
poor substrate for the multidrug resistance
P-glycoprotein efflux pump
 Clinical use
 In combination with prednisone in the
second-line therapy of hormone-
refractory metastatic prostate cancer
 Adverse effects
 Neurotoxicity
 Allergic reactions
Ixabepilone
 Semisynthetic epothilone B analog
 MOA:
 Microtubule inhibitor
 M phase of the cell cycle
 Clinical use
 Metastatic breast cancer
 Adverse effect
 Myelosuppression, hypersensitivity
reactions, and neurotoxicity
Eribulin
 Synthetic analog of halichondrin B
 Microtubule inhibitor
 Block in the G2-M phase
 Metastatic breast cancer
EPIPODOPHYLLOTOXINS
TOPOISOMERASE II
INHIBITORS
EPIPODOPHYLLOTOXINS
 Drug
Etoposide
 Semisynthetic derivative of podophyllotoxin
 MOA
 Forms a complex with topoisomerase II
 Leading to inhibition of the functional activity
of topoisomerase II with inhibition of DNA
synthesis and function
 Clinical uses
 Non-Hodgkin’s lymphoma
 Gastric cancer
 Adverse effects
 Hypotension
 Alopecia
CAMPTOTHECINS
TOPOISOMERASE I
INHIBITORS
Camptothecins
 Natural products derived from the
Camptotheca acuminata tree
 Inhibits topoisomerase I
 Key enzyme responsible for cutting and

religating single DNA strands
 Inhibition of this enzyme results in DNA

damage
Topotecan
 Clinical uses
 Small cell lung cancer
 Ovarian cancer
 Adverse effects
Irinotecan
 Prodrug
 Converted to active metabolite in liver
 1000 fold more potent inhibition of
topoisomerase as compared to
Topotecan
 Clinical use
Metastatic colorectal cancer
Gastroesophageal cancer,
non-small cell and small cell lung cancer
 Adverse effects
Myleosuppression
Diarrhea
ANTITUMOR
ANTIBIOTICS
 Anthracycyline
Doxorubicin
Danorubicin
Idarubicin
Epirubicin
Mitoxantrone
 Mitomycin
 Bleomycin
Anthracycylines
 Isolated from Streptomyces peucetius
var caesius
 Most widely used cytotoxic anti-cancer

drugs
Mechanism of action
 Four major mechanims
Inhibition of topoisomerase II
Generation of free radicals
○ Semiquinone free radicals and
○ Oxygen free radicals
 through an iron-dependent, enzyme-mediated reductive
process
High-affinity binding to DNA through intercalation,
○ with consequent blockade of the synthesis of DNA
and RNA, and DNA strand scission
Binding to cellular membranes to alter fluidity
and ion transport
 Administered via IV route
 Metabolized in liver
 Upto 50% drug is eliminated in feces
 Administered on an every-3-week
schedule
 Low dose can be given weekly, or 72 to
96 hours
Doxorubicin
 Clinical uses
 Breast cancer
 Hodgkin’s and non-hodgkin’s lymphoma
 Ovarian cancer
 Thyroid cancer
 Wilms’ tumor
 Neuroblastoma
 Adverse effects
 Nausea
 Red urine (not hematuria)
 Cardiotoxicity
 Alopecia
 Stomatitis
Daunorubicin
 Clinical uses
 AML
 ALL
 Adverse effects
 Fever
 Red urine (not hematuria)
 Cardiotoxicity
 Alopecia
Idarubicin
 Clinical uses
 AML
 ALL
 CML in blast crisis
 Adverse effects
 Mucositis
 Cardiotoxicity
Mitoxantrone
 Anthracene compound whose structure
resembles the anthracycline ring
 Binds to DNA to produce strand

breakage and inhibits both DNA and
RNA synthesis
 Clinical uses
 Prostate cancer
 Non Hodgkin lymphoma
 Breast cancer
 AML
 Adverse effects
 Nausea and vomting
 Mucositis
 Alopecia
 Cardiotoxicity
 Blue discoloration of fingernails, sclera and urine
Mitomycin
 Antibiotic
 Isolated from Streptomyces caespitosus
 MOA
 Acts as an alkylating agent
Forms cross-links with DNA
 Formation of oxygen free radicals

Which target DNA
 Clinical uses
 Superficial bladder cancer
 Gastric cancer
 Breast cancer
 Head and neck cancer (in combination with radiotherapy)
 Adverse effects
 Mucositis
 Anorexia and fatigue
 Hemolytic-uremic syndrome
Bleomycin
 MOA
 It acts by binding to DNA, which results in
single and double-strand breaks
 Following free radical formation, and

inhibition of DNA biosynthesis
 Fragmentation of DNA is due to

oxidation of a DNA-bleomycin-Fe(II) complex and
leads to chromosomal aberrations
 Bleomycin is most effective in the G2
phase
 It is also active against non-dividing cells

 Clinical uses
 Adverse effects
 Allergic reactions
 Fever
 Hypotension
 Skin toxicity
 Pulmonary fibrosis
 Mucositis
 Alopecia
MISCELLANEOUS
ANTICANCER
AGENTS
 Tyrosine kinase inhibitors
Imatinib
Dasatinib
Nilotinib
Bosutinib
Ponatinib
Ertolinib
Afatinib
Osimertinib
 Growth factor receptor inhibitors
 Epidermal growth factor receptor (EGFR) inhibitors
○ Cetuximab
○ Panitumumab
○ Necitumumab
 Vascular endothelial growth factor (VEGF) inhibitors
○ Bevacizumab
○ Ziv-aflibercept
○ Ramucirumab
 Multiple growth factor receptor inhibitors
○ Sorafenib
○ Sunitinib
○ Pazopanib
TYROSINE KINASE
INHIBITORS
Imatinib
 MOA
 Inhibits Bcr-Abl tyrosine kinase and
other receptor tyrosine kinases,
including
PDGFR, and
c-kit
 Prevents phosphorylation of the kinase

substrate by ATP
 Clinical uses
 CML
 Gastrointestinal stromal tumor (GIST)
 Philadelphia chromosome- positive ALL
 Adverse effects
 Fluid retention with ankle and periorbital edema
 Diarrhea
 Myalgias
 Congestive heart failure
Dasatnib
 Oral inhibitor of several tyrosine kinase receptors, including
 Bcr-Abl
 Src
 c-kit
 PDGFR-α
 Overcomes imatinib resistance

 Resulting from mutation in Bcr Abl
 Approved for
 CML
 Philadelphia chromosome-positive (Ph+) acute
lymphoblastic leukemia (ALL)
Nilotinib
 Inhibits following tyrosine kinase receptors
Bcr-Abl
c-kit
PDGFR-β
 Overcomes imatinib resistance resulting

from Bcr-Abl mutations
 Approved for
CML
Bosutinib
 Inhibitor of the Bcr-Abl tyrosine kinase
 Retains activity in 16 of 18 imatinib-resistant Bcr-Abl mutations
 Not effective against

 T315I and V299L mutations
 Approved for
 CML
 Adverse effects
 Nausea and vomiting
 Diarrhea
 Fluid retention
 Myelosuppression
 Skin rash
 Hepatotoxicity
Ponatinib
 Inhibitor of the
Bcr-Abl tyrosine kinase
Several other tyrosine kinase receptors
 Inhibits all known mutant forms of BCR-

ABL
 Approved for
CML
Erlotinib
 Inhibits EGFR tyrosine kinase leading to inhibition of
EGFR signaling
 Clinical uses
 Adverse effects
 Diarrhea
 Skin rash
 Anorexia
 Interstitial lung disease
GROWTH FACTOR
RECEPTOR
INHIBITORS
EGFR INHIBITORS
 EGFR member of the erb-B family of growth
factor receptors
 Overexpressed in a number of solid tumors
 Activation of the EGFR signaling pathway results
in
downstream activation of several key cellular events
involved in
○ Cellular growth and proliferation
○ Invasion and metastasis
○ Angiogenesis
 EGFR inhibitors block this downstream activation
of different pathways
Cetuximab
 Chimeric monoclonal antibody
 Clinical uses
 Head and neck cancer (used in combination with radiotherapy)
 Adverse effects
 Infusion reaction
 Skin rash
 Hypomagnesemia
 Fatigue
Panitumumuab
 Fully human monoclonal antibody
 Clinical use
 Adverse effects
 Infusion reaction (rarely)
 Skin rash
 Hypomagnesemia
 Fatigue
Necitumumab
 Fully human monoclonal IgG1 antibody
 Clinical use
 In combination with gemcitabine and
cisplatin chemotherapy for the treatment
of squamous NSCLC
 Adverse effects
 Similar to other EGFR inhibitors
VEGF INHIBITORS
 VEGF important angiogenic growth
factor
 Growth of both primary and metastatic

solid tumors requires an intact
vasculature
 VEGF inhibitors target this angiogenesis

Bevacizumab
 Recombinant humanized monoclonal
antibody
 Clinical uses
 Breast cancer
 Renal cell cancer
 Glioblastoma multiformae
 Adverse effects
 Hypertension
 Infusion reaction
 Arterial thromboembolic events
 Gastrointestinal perforations
 Wound healing complications
 Bleeding complications
 Proteinuria
Ziv-aflibercept
 Inhibits binding of VEGFA, VEGF-B, and
placental growth factor (PlGF), to
VEGFR leading to inhibition of VEGF
signaling;
 Inhibits tumor vascular permeability
 Clinical use
 Adverse effects
 Hypertension
 Arterial thromboembolic events
 Gastrointestinal perforation
 Wound healing complications
 Diarrhea
 Mucositis
 Proteinuria
Other multiple receptor inhibitors
 Sorafenib
 Inhibits multiple RTKs, including
raf kinase,
VEGF-R2,
VEGF-R3, and
PDGFR-β
○ leading to inhibition of
 angiogenesis,
 invasion, and
 metastasis
 Clinical uses
 Hepatocellular cancer
 Adverse effects
 Nausea
 Hypertension
 Skin rash
 Fatigue and asthenia
 Hypophosphatemia
 Sunitinib and pazopanib
 Inhibits multiple RTKs, leading to

Inhibition of angiogenesis
Invasion
Metastasis
 Clinical uses
 GIST
 Adverse effects
 Hypertension
 Skin rash
 Fatigue and asthenia
 Cardiac toxicity leading to
Congestive heart failure in rare cases

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Anti Cancer Drugs

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Dr Shabzain Ishrat

ANTI CANCER DRUGS

 A normal cell turns into a cancer cell

 The main genetic lesions being:

 Compartment B consists of resting cells

 Compartment C consists of cells that are

 In many cases, the antiproliferative action is

 Cell cycle–nonspecific (CCNS) drugs:

Topoisomerase I inhibitors (G2-M)

Antitumor antibiotics (G2–M phase)

Vinca alkaloids (M phase)

Antimicrotubule inhibitor (M phase)

 Folates are essential for the synthesis of

 Methotrexate inhibits dihydrofolate

 FH4 functions as an essential cofactor

 Activity in the S phase of the cell cycle

 Also forms metabolites like 6- methylmercaptopurine

 Fludarabine in its trisphosphate form inhibits DNA

 This metabolite is then converted to 5′-deoxy-5-fluorouridine by

 Inhibits ribonucleotide reductase with

 Incorporation of gemcitabine triphosphate

 Form a carbonium ion-a cation, which is highly reactive

 Cyclophosphamide is one of the most widely used

 Occur primarily in rapidly growing tissues such as

 Potent vesicants and can damage tissues at the site of

 ACUTE ADVERSE EFFECTS

 ACUTE ADVERSE EFFECTS

 ACUTE ADVERSE EFFECTS

 ACUTE ADVERSE EFFECRS

 ACUTE ADVERSE EFFECTS

 ACUTE ADVERSE EFFECTS

 These drugs cause

 Alopecia and hemorrhagic cystitis occasionally occur with

 Busulfan is associated with

 ACUTE ADVERSE EFFECTS

 ACUTE ADVERSE EFFECTS

 Acute Adverse effects

 Delayed adverse effects

 ACUTE ADVERSE EFFECTS

 DELAYED ADVERSE EFFECTS

 Acute adverse effects

 Delayed adverse effects

 Acute adverse effects

 Delayed adverse effects

 ACUTE ADVERSE EFFECTS

 Delayed adverse effects

 Delayed adverse effects

 Acute adverse effects

 Taxanes and other mictrotubule synthesis

 Disrupts assembly of microtubules,

 Work in the M phase of the cell cycle

 Cell division arrests in metaphase and cell

 Delayed adverse effects

 Achieving a similar effect to that of the

 Differs from paclitaxel by:

 Useful for treating multidrug-resistant

 Semisynthetic derivative of podophyllotoxin

 Key enzyme responsible for cutting and

 Inhibition of this enzyme results in DNA

 Most widely used cytotoxic anti-cancer

 Binds to DNA to produce strand

 Formation of oxygen free radicals

 Following free radical formation, and