discussed about newer chemical entities in the cancer treatment such as ibrutinib, avastin, nolvadex, mozobil, xeloda, jevtana,femara,letrozole,sutent etc and mechanism of action of various drugs used under there categories.

1. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
NEW DRUGS OF CANCER IN THE RECENT YEAR [10]
1) Ibrutinib
This drug used for the treatment of patients with chronic lymphocytic leukemia
(CLL). Treatment of activated CLL cells with ibrutinib resulted in inhibition of Btk
tyrosine phosphorylation and also effectively abrogated downstream survival
pathways activated by this kinase including ERK, PBK and Nf-KB. It also inhibited
proliferation of CLL cells invitro.[11]
This drug is used for the treatment of
chronic lymphocytic leukemia.
2) Avastin
This drug used for treatment of renal cell carcinoma. Avastin is a recombinant
humanized monoclonal antibody that produces angiogenesis. Acts by inhibiting
vascular endothelial growth factor (VEGF-A). VEGF-A is a chemical signal that
stimulates angiogenesis in variety of disease especially cancer. [12]
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2. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
3) Nolvadex (Tamoxifen)
This drug used for breast cancer. Tamoxifen itself is a prodrug. It is
metabolized in liver cytochrome p450 isoform CYP2D6 and CYP3A4 in to active
metabolites such as 4-hydroxy tamoxifen. It acts as estrogen receptor antagonist so
that transformation of estrogen responsive gene is inhibited. 4-hydroxy tamoxifen
bind to ER, the ER / tamoxifen complex recruits other protein known as co-repressor
and then bind to DNA to gene expression.[13]
4) Mozobil
This drug is used for treatment of non-Hodgkin’s lymphoma and multiple
myeloma. Mozobil is a hematopoietic stem cell mobilizer and inhibitor of the CXCR4
chemokine receptor. It blocks the binding of the CXCR4 cognate ligand, stromal cell-
derived factor-1a (SDF-1a). SDF-1a and CXCR4 are recognized to play a role in the
trafficking and homing of human hematopoietic stem cells to the marrow
compartment. Once in the marrow, stem cell CXCR4 can act to help anchor these
cells to the marrow matrix, either directly via SDF-1a or through the induction of
other adhesion molecules. [14]
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3. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
5) Xeloda
This drug is used for the treatment of metastatic colorectal cancer
.Capecitabine is metabolized 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 and
RNA during gene expression. [15]
6) Jevtana (cabazitaxel)
This drug is used for the treatment of prostate cancer. They bind to
tubulin and promote its assembly into microtubules while simultaneously inhibiting
disassembly. Stabilizes microtubules, which results in the inhibition of mitotic and
interphase cellular function.
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4. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
7) Femara (Letrozole)
This drug is used for treatment of breast cancer. Estrogens are
produced by the conversion of androgens through the activity of the aromatase
enzyme. Estrogens then bind to an estrogen receptor, which causes cells to divide.
Letrozole prevents the aromatase from producing estrogens by competitive, reversible
binding to the heme of its cytochrome P450 unit. The action is specific, and letrozole
does not reduce production of mineralocorticosteroids. [16]
8) Sutent (Sunitinib)
This drug is used for treatment of kidney cancer and GI stromal tumors.
Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases
(RTKs). These include all receptors for platelet-derived growth factor (PDGF-Rs) and
vascular endothelial growth factor receptors (VEGFRs), which play a role in both
tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these
targets therefore leads to both reduced tumor vascularization and cancer cell death,
and ultimately tumor shrinkage. Sunitinib also inhibits KIT (CD117) the RTK that
(when improperly activated by mutation) drives the majority of gastrointestinal
stromal cell tumors.
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5. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
9) Camptosar (Iriotecan)
This drug is used for the treatment of colon of rectal cancer. Iriotecan
is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then
inactivated by glucouridination by uridine diphosphate glucoronosyltransferase 1A1
(UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38
eventually leads to inhibition of both DNA replication and transcription.
10) Zytiga (Abiraterone acetate)
This drug is used for the treatment of prostate cancer. Abiraterone
inhibits 17 α-hydroxylase/C17,20 lyase (CYP17A1), an enzyme which is expressed in
testicular, adrenal, and prostatic tumor tissues. CYP17 catalyzes two sequential
reactions: (a) the conversion of pregnenolone and progesterone to their 17-α-hydroxy
derivatives by its 17 α-hydroxylase activity, and (b) the subsequent formation of
dehydroepiandrosterone (DHEA) and androstenedione, respectively, by its C17,20
lyase activity.
11) Sensipar (Cinacalcet)
This drug is used for the treatment of secondary hyper parathyroidism and
hyper calcemia in parathyroid carcinoma patients. The calcium-sensing receptors
onthe surface of the chief cell of the parathyroid gland is the principal regulator of
parathyroid hormone secretion (PTH). Cinacalcet increases the sensitivity of calcium
APSC, Pariyaram 32

6. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
receptors on parathyroid cells to reduce parathyroid hormone (PTH) levels and thus
decrease serum calcium levels.
12) Ethyol (Amifostine)
This drug is used for the treatment for xerostomia (dry mouth) due to
radiation. Instead cells, amifostine detoxifies reactive metabolites of platinum and
alkylating agents, as well as scavenges free radicals. Other possible effects include
accelerated DNA repair, induction of cellular hypoxia, inhibition of apoptosis,
alteration of gene expression and modification of enzyme activity.
13) Gemzar ( gemcitabine Hcl)
This drug is used for the treatment of lung cancer. Gemcitabine is
metabolized by nucleoside kinases to diphosphate (dFdCDP) and triphosphate
(dFdCTP) nucleosides. Gemcitabine diphosphate inhibits ribonucleotide reductase, an
enzyme responsible for catalyzing the reactions that generate deoxynucleoside
triphosphates for DNA synthesis, resulting in reductions in deoxynucleotide
concentrations, including dCTP.
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7. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
14) Pomalidomide
This drug is used for the treatment of patients with multiple myeloma.
Pomalidomide directly inhibits angiogenesis and myeloma cell growth. This dual
effect is central to its activity in myeloma, rather than other pathways such as TNF
alpha inhibition, since potent TNF alpha inhibitors including rolipram and
pentoxifylline do not inhibit myeloma cell growth nor angiogenesis.
NEW FDA APPROVED DRUGS IN RECENT YEAR
FDA APPROVED DRUGS IN 2014[17]
1) Beleodaq (belinostat) :
This drug is used for the treatment of relapsed or refractory
peripheral T-cell lymphoma. This drug is approved by FDA in 2014.
2) Cyramza (ramucirumab) :
This drug is used for the treatment of gastric cancer. This
drug is approved by FDA in 2014 .
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8. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
3) Zydelig (idelalisib):
This drug is used for the treatment of relapsed CLL,
follicular B-cell NHL and small lymphocytic lymphoma .This drug
approved in 2014.
4) Zykadia (ceritnib) :
This drug is used for the treatment of ALK+ metastatic
non-small cell lung cancer. This drug approved in 2014.
FDA APPROVED DRUGS IN 2013[18]
1) Gazyva (obintuzumab) :
This drug is used in combination with chlorambucil to treat
patients with previously untreated chronic lymphocytic leukemia (CLL).
This drug approved in 2013.
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9. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
2) Gilotrif (afatinib) :
This drug is used for patients with late stage (metastatic) non-
small cell lung cancer (NSCLC) whose tumors express specific types of
epidermal growth factor receptor (EGFR) gene mutations, as detected by
an FDA-approved test.
3) Mekinist (trametinib) :
This drug is used to treat patients whose tumors express the
BRAF V600E or V600K gene mutations. This drug is approved in 2013.
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10. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
4) Tafinlar (dabrafenib) :
This drug is used to treat patients with melanoma whose
tumors express the BRAF V600E gene mutation.This drug approved in
2013.
5) Xofigo :
This drug is used o treat men with symptomatic late-stage
(metastatic) castration-resistant prostate cancer that has spread to bones
but not to other organs. This drug approved in 2013.
FDA APPROVED DRUGS IN 2012 [19]
1) Cometriq (cabozantinib) :
This drug is used To treat medullary thyroid cancer that
has spread to other parts of the body.This drug approved in 2012.
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11. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
2) Stirvarga (regorafenib) :
This drug is used to treat patients with colorectal cancer
that has progressed after treatment and spread to other parts of the body.
This drug approved in 2012.
3) Xtandi (enzalutamide) :
This drug is used to treat men with late-stage (metastatic)
castration-resistant prostate cancer that has spread or recurred, even with
medical or surgical therapy to minimize testosterone. This drug approved
in 2012.
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12. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
4) Perjeta (pertuzumab) :
This drug is used to treat patients with HER2-positive
late-stage (metastatic) breast cancer. This drug approved in 2012.
5) Erivedge (vismodegib) :
This drug is used to treat adult patients with basal cell
carcinoma, the most common type of skin cancer.This drug approved in
2012.
6) Lnlyta (axitinib):
This drug is used to treat patients with advanced kidney
cancer (renal cell carcinoma) who have not responded to another drug for
this type of cancer. This drug approved in 2012.
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13. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
FDA APPROVED DRUGS IN 2011[20]
1) Adcetris (brentuximab vedotin) :
This drug is used For the treatment of Hodgkin lymphoma and
anaplastic large cell lymphoma.
2) Yervoy (ipilimumab) :
This drug is used for the treatment of metastatic
melanoma. This drug approved in 2011.
3) Abstral (fentanyl sublingual tablet) :
This drug is used for the treatment of breakthrough cancer
pain in opioid-tolerant patients.
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14. Recent development in cancer research; A critical review on new chemical Entities New Chemical Entities
4) Afinitor (everolimus) :
This drug is used for the treatment of advanced pancreatic
neuroendocrine tumors. This drug is approved in 2011.
5) Vandetanib :
This drug is used for the treatment of thyroid cancer.
6) Xalkori (crizotinib) :
This drug is used for the treatment of ALK+ non-
small cell lung cancer.
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