Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common known hereditary cause of colon cancer.

BRCA1/BRCA2 are tumor suppressor genes; defects-mutations in these genes lead to defective protein products; correlated with increased risk of breast cancer.

1. Tissue invasion and metastasis (Inactivate E-cadherin) 
2. Inflammatory invasion of microenvironment
3. Evasion of apoptosis (Ex. providing IGF survival factors)
4. Sustained angiogenesis (Ex. Produce VEGF inducer) 
5. Insensitivity to growth inhibitors (Ex. Lose retinoblastoma suppressor) 
6. Limitless replicative potential (Ex. Turn on telomerase) 
7. Self sufficiency in growth signals (ex.activate H-Ras oncogene)

a gene whose product protein is involved in either transforming cells in tissue culture or in inducing cancer in animals.  Most oncogenes are mutant forms of normal genes in control of cell growth or division. 

Ex. Mutant Ras proteins,are hyperactivated forms of Ras, and are the most common genetic alterations detected in human cancer.  Ras pathway plays an important role in tumor growth and is believed to be abnormally activated in one-third of human cancers, including cancers of the pancreas, colon, lung and breast. Up to 90% of human pancreatic cancers are driven by aberrant oncogenic Ras signaling.

Inactivation of Tumor Suppressor Genes/proteins

Example: Inactivate retinoblastoma suppressor (Rb) protein

The Rb protein acts to control whether cells enter G1 or stay in a safer resting state

The retinoblastoma gene encodes a 928–amino acid phosphoprotein, Rb, which arrests cells in the G1 phase.  Rb is phosphorylated and dephosphorylated during the cell cycle; the hyper-phosphorylated (inactive) form predominates in proliferating cells, whereas the hypo-phosphorylated (active) form is generally more abundant in quiescent or differentiating cells.

p53= gatekeeper of cell
p53 activates DNA repair proteins when DNA has sustained damage.

It can also hold the cell cycle at the G1/S regulation point on DNA damage recognition.

It can initiate apoptosis if the DNA damage proves to be too much to handle by repair machinery.

•p53 exists in non-stressed cells at a very low concentration.
•  Under stress conditions, p53 protein accumulates in the cell, binds induces transcription of various genes that are involved in cell-cycle control, apoptosis, DNA repair, differentiation and senescence.
•  The loss of p53 tumor-suppressor activity by mutation/deletion or inhibition of p53 allows the proliferation of the cells that are damaged under the stress conditions.
This uncontrolled proliferation can lead to tumor development

Normally under apoptosis conditions the cell is sealed, shrunken, chromatin condenses, non-random DNA fragmentation, complete enzymatic use, viable biosynthesis (parts are re-usable) and the body initiates a phagocytosis response instead of

With necrosis the cell is swollen, leaky, the chromitin clumped, the necrosis is usually localized, truncated enzyme activity, body initiates an inflammation response, non viable biosynthesis, and DNA fragmentation is smeared and random.  

Normal cells divide ~ 20-50 times in the laboratory, then they become senescent (lose ability to divide)

Cancer cells divide indefinitely

Senescence is caused by loss of telomerase activity…. but….cancer cells reactivate telomerase and become immortal!!

Angiogenesis is associated with degradation and reformation of the vascular basement membrane.

• a | In response to growth factors and matrix metalloproteinases (MMPs), the vascular basement membrane (VBM) undergoes degradative and structural changes. This transition from mature VBM to provisional matrix promotes the proliferation and migration of vascular endothelial cells. Growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), are released from the basement membrane, and are also produced by tumor cells, fibroblasts and immune cells.
• b | This induces formation of an intermediate, and then a new (mature) vascular basement membrane. Together with the vascular endothelial cells and pericytes, the VBM mediates formation of a new blood vessel. The degraded VBM during this process has a crucial role in regulating angiogenesis.

Iressa - blocks production of VEGF

Avastin - Neutralizes VEGF

Sutent - Blocks receptor for VEGF

The only problem is the fact that cancers are highly variable. Breast cancer alone has up to 6 angiogenesis stimulating growth factors. (VEGF, bFGF, TGF beta 1, PLGF, PD- ECGF, and pleiotrophin) 

• Many types of cadherins; cadherins within one class will only bind to themselves.  For example, an N-cadherin will bind only to another N-cadherin molecule.
• Because of this specificity, groups of cells that express the same type of cadherin molecule tend to cluster together during development, while cells expressing different types of cadherin molecules tend to separate

•  

• Changes in adhesion are prominent during the metastatic journey. At the onset of this process, cancer cells lose E-cadherin-dependent intercellular adhesions, acquire a migratory phenotype, penetrate the basement membrane, and invade the interstitial matrix. Tumor angiogenesis then allows cancer cells to enter the bloodstream, either directly or through the lymphatic system, by a process called intravasation. In the circulation, tumor cells form small aggregates with platelets and leukocytes. Finally, after stopping in the microcirculation of the target organ, tumor cells exit the bloodstream, by a process called extravasation, and undergo local expansion.
• Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis.
• E-cadherin inactivation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility.
• This in turn may allow cancer cells to “break off” cross the basement membrane and invade surrounding tissues

Uses the body surface area. BSA is believed to be a more accurate measure that eliminates “adipose” effects. Criticized for not taking into account interpatient variation in pharmacokinetics and pharmacogenetics.

X= Sqaure root of [ weight(in kg) x height (in cm) / 3600] 

The commonly accepted 50th percentiles for BSA are 1.94 m2 for adult men and 1.69 m2 for adult women

1. Chemotherapeutics generally have a narrow therapeutic index 

2. It can produce adverse effects (off site issues) 

- bone marrow suppresion, alopecia, mucositis, phlebitis, cysistis, renal failure, myalgia, neuropathy, diarrhea. etc...

3. Cancer cells can become resistant to chemotherapy 

4. Chemotherapeutics act at various stages of cell cycle

Alkylating Agents

Antimetabolites

Mitotic inhibitors

Antitumor antibiotics

Kinase Inhibitors (oral)

Hormone Antagonists-Inhibitors (oral)

Targeted protein therapeutics (Mab’s)

The 4 Classes 

1. Nitrogen Mustards (ex: cyclophosphamide) 

2. Triazenes (Ex. Temozolomide) 

3. Nitrosoureas (Ex. Carmustine) 

4. Platinums (Ex. Cisplatin) 

They are cell-cycle NON-SPECIFIC

All are electrophilic molecules that covalently modify nucleic acid bases

Monofunctional

--Cause single strand DNA breaks

Bifunctional

--Inhibit DNA replication and transcription by crosslinking DNA

Several are PROdrugs and require biotransformation by the liver so they are taken orally and first pass metabolism is required. 

(Ex. Cyclophosphamide is metabolized by CYPB6, 2C9, 3A4 to become a phosphroamide mustard (active compound) There is another metabolite waste product form called Acrolein which is toxic to the bladder so MESNA is given along with cyclophosphamide to scavenge the acrolein and protect the bladder. 

Trade Name: Cytoxan or Neosar 

Type: anti-cancer agent 

Function : An anti-cancer alkylating agent that is a nitrogen mustard. It covalently modifies nucleic acid bases 

Major Use: treats acute lymphocytic leukemia, chronic lymphocytic leukemia, non-hodgkin lymphoma, myeloma, breast, testis, ovary, lung, and cervix cancers 

Extra Info: 

• Hemorrhagic cystitis due to irritation of the bladder mucosa by urinary metabolites, (Acrolein)
• The most severe dose-limiting toxicity of cyclophosphamide is a cardiac toxicity (fatal)
• The syndrome usually presents with severe cardiac failure beginning approximately 10 days after drug administration, with a dilated heart and low electrocardiogram voltage. There is a characteristic pathologic picture of edema, interstitial hemorrhage and cardiac necrosis 

• Prodrugs  which decompose to alkylating agents producing interstrand cross-links in DNA. 

Trade Name :  GLIADEL 

Type :nitrosourea alkylating agent 

Function : once dissolved (activation) and absorbed by tumor tissue the carmustine molecule is absorbed and acts to produce interstrand crosslinking with DNA.

Major Use : this wafer is indicated for treatment of Glioblastoma Multiforme. (brain cancer). The wafers are inserted into the brain around the tissue of action and once they have dissolved they release 

Extra Info :The wafer is made of biodegradable polymer and Carmustine

(BCNU) which is gradually absorbed by the tumor tissue.

The wafer is placed inside adjacent to the site where the tumor was removed from brain surgically. Up to 8 wafers are used. 

Trade Name : Dacarbazine

Type : Triazine alkylating agent 

Function : methylates DNA once activated to a methyldiazonium ion (so it is a prodrug) 

Major Use : treats melanoma and Hodgkin lymphoma 

Extra Info : It is Part of the polychemotherapy regimen:

Temozolomide 

Cisplatin–DNA adducts cause various cellular responses, such as replication arrest, transcription inhibition, cell-cycle arrest, DNA repair and apoptosis.

Types

1. cisplatin 

2. Carboplatin 

3. Oxaliplatin 

Trade Name :

Type : platinum alkylating agent 

Function :The platinum atom of cisplatin binds covalently to the N7 position of purines to form 1,2- or 1,3-intrastrand crosslinks, and interstrand crosslinks.
Cisplatin–DNA adducts cause various cellular responses, such as replication arrest, transcription inhibition, cell-cycle arrest, DNA repair and apoptosis 

Major Use : Used to treat testicular and ovarian cancer. Also increasingly used against bladder, cervical and lung tumors as well as tumors in the head and neck.

Cisplatin is one of the largest grossing anticancer agents in the world earning > 200 billion dollars world-wide

---They kill cells in S phase (s-phase specific) 

The 3 Types 

1. Folic Acid Antagonists (Methotrexate) 

2. Purine Analogs (Clorfarabine) 

3. Pyrimidine Analogs (5-FU) 

Trade Name : Rheumatrex

Type : folic acid antagonist form of anti-metabolite 

Function : It is a competitive inhibitor of folic acid. Depletion of FH4 in cell --> dTMP --> inhibition of DNA synthesis 

Major Use : 

Trade Name : ALTIMA 

Type : folic acid antagonist 

Function :

Major Use :when given with cisplatin, is the first and only chemotherapy drug to be approved by the FDA for the treatment of patients with malignant pleural mesothelioma (MPM) –cancer which affects lining surrounding lung; when surgery is not an option.  (asbestos linked cancer). Other indications.

Trade Name : Folotyn 

Type : Folic Acid Antagonist 

Function :designed for improved cellular transport and to have greater intracellular drug retention through the enhanced formation of polyglutamylated conjugates

Major Use : for relapsed or refractory peripheral T-cell lymphoma 

Trade Name : Cytosar U 

Type : pyrimidine analog anti-metabolite 

Function :

It is activated to 5’-monophosphate (AraCMP)

Again, a fraudulent nucleotide

Major Use :

Extra Info 

Trade Name : Gemzar 

Type : pyrimidine analog anti-metabolite 

Function :

• ¨Inhibits DNA synthesis; fraudulent nucleoside; converted to nucleotides by sequential phosphorylation to triphosphate.
• ¨Incorporated into DNA growing chain.
• ¨Prevents DNA repair by masked termination; permits one more nucleotide to pair before termination of the replication process. This means that the gemcitabine nucleotide is less susceptible to excision repair by exonuclease enzymes, making DNA repair more difficult (masked termination).

Major Use : treatment of pancreatic cancer 

Trade Name : Xeloda 

Type : pyrimidine analog antimetabolite 

Function : 

Capecitabine is a prodrug of 5-FU.

Capecitabine crosses the gastrointestinal barrier intact and is rapidly absorbed. It was designed to avoid being metabolized by thymidine phosphorylase in the small intestine.

Major Use :

Trade Name : Adriamycin 

Type : anthracycline anti-tumor antibiotic 

Function :

oCause apoptosis of cancer cells by a complex network of events which include:

oColor of drug is “blood-red”

Major Use : most used broad spectrum anti-cancer agent 

Extra Info:

• Cardiotoxicity (cumulative!):  characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species, generated by the interaction of doxorubicin with iron, can then damage the myocytes (heart cells).  Reversible damage with low dose; high dose can lead to irreversible heart damage.
• Dexrazoxane (Zinecard) is an iron chelator used in conjunction with Doxorubicin.
• Lifetime dose of DOX should not exceed 550 mg/m2

Trade Name : Doxil 

Type : anthracyclin anti-tumor drug 

Function :

• a reformulated version of doxorubicin. DOXIL takes the active agent doxorubicin and places it into a fat bubble called a liposome (Stealth liposomes) and another layer of PEG.
• This coating allows DOXIL to evade detection and destruction by the immune system, which increases the time the drug is in the body.
• The majority of the drug stays inside the liposome while in the blood (at least 90%). Therefore, DOXIL has more time to reach the tumor tissue, where the medication slowly diffuses out.

Major Use : anti-cancer agent 

Extra Info:Administered by IV infusion (ovarian cancer; AIDS related Kaposi’s sarcoma, multiple myleloma

These are natural products that are derived from plants but most are semi-synthetic derivates of natural products (meaning we modify them a bit) 

Types: 

1. Vinca Alkaloids (ex. vinblastine) 

2. Podophylloxins (Ex. etoposide)

3. Camptothecins (Ex. Ironotecan) 

4. Taxanes (ex. Paclitaxel)

Trade Name : Abraxane 

Type : Albumin bound taxol. uses albumin, a human protein, to deliver the chemotherapy

Function :

Major Use :

Extra Info.

It does not contain use emulsifiers, like Cremophor. This eliminates the need for premedication with steroids or antihistamines for hypersensitivity reactions caused by these solvents. Plus ABRAXANE is administered in just 30 minutes (compared to 3 hours for solvent-based paclitaxel)

Indicated for  metastatic breast cancer

Mechanism of action of aromatase inhibitors and tamoxifen – Tamoxifen competes with estradiol for estrogen receptor (ER) binding, whereas aromatase inhibitors reduce the synthesis of estrogens from their androgenic precursors. (estradiol) 

Aromatase Inhibitors

1.Exemestane (Aromasin) 

2. Anastrozole (Arimidex) 

3. Letrozole (Femara) 

Trade Name : Tamoxifen 

Type : selective estrogen receptor modulator (SERM) 

Function : antagonist of the estrogen receptor in breast tissue (its selective). G1 cell cycle arrest; thus it is a growth inhibitor 

Major Use : Can prevent or delay the formation of breast cancer in high risk women (49% risk reduction in clinical trials) 

Extra Info: the first targeted anti cancer drug. It is a prodrug. 

• Although a estrogen receptor antagonist it is an endometrium agonist. 
• Adverse effects: thromboembolitic events and higher risk of causing endometrial cancer. 
• METABOLISM
  • Sequential biotransformation of tamoxifen (TAM) to endoxifen in humans. Tamoxifen is predominantly N-demethylated by the CYP3A enzyme to N-desmethyl-tamoxifen, which is a major primary tamoxifen metabolite quantitatively. (At steady state, the plasma concentration of this metabolite is more than 1.5-fold higher than that of tamoxifen after 20-mg/d treatment with tamoxifen.) This metabolite undergoes multiple oxidations including 4-hydroxylation by CYP2D6 to endoxifen. Tamoxifen 4-hydroxylation via multiple CYPs to 4-hydroxytamoxifen represents a minor primary metabolic route of tamoxifen.

• Effect of CYP2D6 genotype and concomitant use of CYP2D6 inhibitors on plasma endoxifen concentration after 4 months of tamoxifen treatment revealed that  patients may not be getting a “therapeutic dose” of tamoxifen—due to genotype or drug-drug interactions

Trade Name : EVISTA 

Type : SERM (selective estrogen receptor modulator) 

Function :

Major Use : is indicated for the treatment of osteoporosis and for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.

(orally active

Extra Info 

Trade Name : Aromasin 

Type : aromatase inhibitor. Steroidal and an irreversible inhibitor of estrogen receptor. 

Function : 

Major Use : Approved for post-menopausal women who have had estrogen receptor positive early breast cancer AND have been on Tamoxifen for 2 or 3 years. 

Extra Info 

Should be taken after a meal 

Trade Name : Arimidex and Femara 

Type : Non-steroidal aromatase inhibitor. Reversible inhibitor or estrogen receptor 

Function :

Major Use : Indicated for adjuvant treatment of postmenopausal women (ER positive) ; first-line for locally advanced metastatic breast cancer; advanced breast cancer following tamoxifen therapy

Extra Info These are VERY potent compounds. Arimidex is only available in 1.0 mg and Femara as 2.5 mg tablets. 

Trade Name : Zolinza 

Type : HDAC (histone deacetyl-ase) inhibitor. 

Function :Excess deacetylation of histones by abnormal HCAC activity present in some tumor cells and by inhibiting HDAC—results in accumulation of acetylated histone—upregulates gene trasnscription –leads to apoptosis of cancer cells.

Major Use :Indicated for treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies

Extra Info 

• Remember, cell surface receptors have two components: extracellular and intracellular.  Growth factors (like EGF [epidermal growth factor]) bind its receptor [EGFR] and send a signal to inside of cell.
• This activates the “kinase” portion of the receptor to phosphorylate and begin the process of signal transduction to nucleus (transcription).
• Inhibitors—act by inhibiting specfic tyrosine kinases—prevent phosphorylation, interfere with cell signalling, growth, proliferation of cancer cells. 
  • Work from the inside of a cell!
  • Orally Active!
  • Inhibit binding of ATP to tyrosine kinase; no phosphorlation
• Receptors from the HER family: HER1 or EGFR, HER2 or ErbB2, HER3, and HER4.  Similar, but distinct.  They bind specific growth factors
• Tyrosine Kinase inhibitors work inside the cell; Mab’s work outside the cell. SAME PROTEIN TARGET, but different sites of action

• After binding with their ligand (growth factor), tyrosine kinases are activated and phosphorylation occurs.  This signal leads ultimately to  increased cell proliferation, angiogenesis, invasion and metastasis.  TK inhibitors like erlotinib and gefitinib inhibit the TK activity of HER1/EGFR.  Thus, they are called HER1/EGFR TK inhibitors.

  The MAb cetuximab binds to EGFR with high specificity and with a higher affinity than EGF.  This too shuts down signal transduction

Trade Name : Gleevec

Type : Bcr-Abl targeted tyrosine kinase + others 

Function : Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

• Extra Info:  
• Imatinib is a tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, abnormal kinase created by the Philadelphia chromosome  (Ph) abnormality in chronic myeloid leukemia (CML).  Abnormal fusion protein.
• The Ph chromosome is an abnormally short chromosome 22 that is involved in a translocation (an exchange of material) with chromosome 9. This translocation takes place in bone marrow cells, and, gives rise to leukemia.
• Abnormal Philadelphia (Ph) chromosome identified in over 90% of CML, 20% of adult ALL and 5% of pediatric ALL patients
• 
  
• Should be taken with food to prevent gastrointestinal irritation

Trade Name : Iressa 

Type : HER1 targeted tyrosine kinase inhibitor 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Extra Info 

Trade Name : Tarceva 

Type : HER1 tyrosine kinase inhibitor 

Function : Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Extra Info: "Tarceva prolonged survival by 37% in clinical trials, however, this was only an average of 2 months when compared to a placebo group"

When given in combination with gemcitabine it extended life 2 WEEKS longer than placebo group 

Used for metastatic pancreatic cancer 

Trade Name : Nexavar 

Type : Raf tyrosine kinase targeted inhibitor + others 

Function : Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use: renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC)

Extra Info 

Trade Name : Sutent 

Type : VEGFR tyrosine kinase inhibitor 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use:  (RCC) renal cell carcinoma and (GIST) gastrointestinal stromal tumor

Trade Name : Sprycel 

Type : Bcr-Abl tyrosine kinase inhibitors + others 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use: CML and ALL  

Take with antacids 2 hours before use to prevent interactions 

Trade Name : Tykerb 

Type : HER1 and HER2 tyrosine kinase inhibitors 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use: Advanced or metastatic breast cancer  

Trade Name : Tasigna 

Type : Bcr-Abl tyrosine kinase inhibitors + others 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use: CML  

Trade Name : Voltrient 

Type : VEGFR and others 

Function :Prevents phosphorylation, interferes with cell signaling, growth, and proliferation of cancer cells by working inside the cell. Inbiting binding of ATP to tyrosine kinase then there is no phosphorylation

Major Use : RCC (renal cell carcinoma) 

Trade Name : Rituxan 

Type : Chimeric 

Target: CD-20 

Indication : NHL (Non-Hodgkin Lymphoma) 

Extra Info : 

Trade Name : Herceptin 

Type : Humanized 

Target: HER2 

Indication: Breast Cancer 

Extra Info 

• Humanized MAb, binds to HER-2 receptors, prevents HER-2 activation of kinases; shuts down cell growth signals.
• Indicated as part of many treatment regimens containing doxorubicin, cyclophosphamide, and paclitaxel, adjuvant treatment of patients with HER2 node‑positive breast cancer.
• As a single agent following anthracycline based therapy, or with docetaxel and carboplatin; with lapatinib.

• Trastuzumab (Herceptin) binds with high affinity and specificity to the extracellular domain of HER2. Lapatinib (Tykerb) inhibits both the HER1 and HER2 tyrosine kinases. Trastuzumab and lapatinib impair phosphorylation and signal transduction

• Black box warnings:
  • Cardiomyopathy
  • Infusion reactions
• Most patients with breast cancer receiving trastuzumab-containing regimens experience disease progression.
  Preclinical data and data from phase I trials also indicated that lapatinib had synergistic effects with trastuzumab in HER2-positive breast cancer cells.
  Clinical response was observed in patients with HER2-postive tumors but not in those with HER1-positive tumors

Trade Name : Mylotarg

Type : Humanized 

Target: CD33 

Indication: ALL 

Extra Info :

Trade Name : Campath 

Type : Humanized 

Target: CD52

Indication: B-cell CLL (chronic lymphoid leukemia) 

Extra Info :

Trade Name : Zevalin 

Type : Murine 

Target: CD20 

Indication: NHL 

Extra Info :

Trade Name : Bexxar 

Type : Murine 

Target: CD20 

Indication: NHL 

Extra Info :

Trade Name : Erbitux 

Type : Chimeric 

Target: HER1 

Indication: colorectal caner or head/ neck cancer 

Extra Info :

**Indicated in combination with radiation therapy for advanced head and neck cancer

Trade Name : Avastin 

Type : Humanized 

Target: VEGF 

Indication: Colorectal, lung, breast, kidney, NSCLC, Brain 

Extra Info :

• VEGF Blocker-
  • Inhibits angiogenesis
• Indicated:
  • MCRC (in combo with IV-5-FU
  • NSCLC ( combo with paclitaxel and carboplatin)
  • MBC (combo with paclitaxel)
• Estimated Half life is about 20 days 
• Black Box Warnings:
  • GI perforations
  • Wound—healing problems
  • Severe bleeding

Trade Name : Vectibix 

Type : Human 

Target: VEGF

Indication: Metastatic Colorectal cancer 

Extra Info :

Trade Name : Arzerra

Type : Human 

Target: CD20

Indication: CLL 

Extra Info :