Bortezomib: is an anti-cancer drug and the first therapeutic proteasome inhibitor to be used in

humans. Proteasomes are cellular complexes that break down proteins. In some cancers, the
proteins that normally kill cancer cells are broken down too quickly. Bortezomib interrupts this
process and lets those proteins kill the cancer cells. The boron atom in bortezomib binds the
catalytic site of the 26S proteasome with high affinity and specificity. In normal cells, the
proteasome regulates protein expression and function by degradation of ubiquitylated proteins,
and also cleanses the cell of abnormal or misfolded proteins. Clinical and preclinical data
support a role in maintaining the immortal phenotype of myeloma cells, and cell-culture and
xenograft data support a similar function in solid tumor cancers.
It is approved in the U.S. and Europe for treating relapsed multiple myeloma and mantle cell
lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with
otherwise refractory or rapidly advancing disease.

Bortezomib:

Trastuzumab, trade name Kadcyla, is an antibody-drug conjugate consisting of the monoclonal

antibody trastuzumab (Herceptin) linked to the cytotoxic agent emtansine (DM1). Trastuzumab alone
stops growth of cancer cells by binding to the HER2/neu receptor, whereas DM1 enters cells and
destroys them by binding to tubulin.

In the United States, ado-trastuzumab emtansine was approved specifically for treatment of HER2-
positive metastatic breast cancer (mBC) in patients who have been treated previously with
trastuzumab and a taxane (paclitaxel or docetaxel), and who have already been treated for mBC or
developed tumor recurrence within six months of adjuvant therapy.

Herceptin (e.g. Rituximab, Trastuzumab):

Flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute
myeloid leukemia, by Tolero Pharmaceuticals, Inc. It has been studied also for the treatment of
arthritis and atherosclerotic plaque formation The target of Flavopiridol is the positive
transcription elongation factor P-TEFβ. Treatment of cells with Flavopiridol leads to inhibition
of P-TEFβ and the loss of mRNA production. Flavonoid is useful to for the treatment of chronic
lymphocytic leukemia (CLL) and acute myeloid leukemia (AML).

Flavopiridol:

Cisplatin is a chemotherapy medication used to treat a number of cancers. This includes

testicular cancer, ovarian cancer, breast cancer, bladder cancer, head and neck cancer, cervical
cancer, lung cancer, mesothelioma, esophageal cancer, brain tumors, and neuroblastoma. It is
used by injection into a vein.

Cisplatin, carboplatin, and oxaliplatin enter cells by diffusion, and by an active Cu 2+

transporter. Inside the cell, the chloride atoms of cisplatin may be displaced and the compound
may be inactivated directly by reaction with nucleophiles such as thiols. Chloride is replaced by
water, yielding a positively charged molecule. In the primary cytotoxic reaction, the aquated
species of the drug then reacts with nucleophilic sites on DNA and proteins. Aquat ion is favored
at the low concentrations of chloride inside the cell and in the urine. High concentrations of
chloride stabilize the drug, explaining the effectiveness of chloride diuresis in preventing
nephrotoxicity. Hydrolysis of carboplatin removes the bidentate cyclo-butane-dicarboxylato
group; this activation reaction occurs slowly.
Cisplatin
6-Thioguanine is a thio analogue of the naturally occurring purine base guanine. 6-thioguanine
utilises the enzyme hypoxanthine-guanine-phospho-ribosyltransferase (HGPRTase) to be
converted to 6-thioguanosine monophosphate (TGMP). High concentrations of TGMP may
accumulate intracellularly and hamper the synthesis of guanine nucleotides via the enzyme
Inosine monophosphate dehydrogenase (IMP dehydrogenase).

TGMP is converted by phosphorylation to thioguanosine diphosphate (TGDP) and

thioguanosine triphosphate (TGTP). Simultaneously deoxyribosyl analogs are formed, via the
enzyme ribonucleotide reductase. The TGMP, TGDP and TGTP are collectively named 6-
thioguanine nucleotides (6-TGN). 6-TGN are cytotoxic to cells by: (1) incorporation into DNA
during the synthesis phase (S-phase) of the cell; and (2) through inhibition of the GTP-binding
protein (G protein), Rac1, which regulates the Rac/Vav pathway. [23] An additional effect may be
derived from the incorporation of 6-thioguanine into RNA. This yields a modified RNA strand
which cannot be read by the ribosomes.

6-TG is a medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia
(ALL), and chronic myeloid leukemia (CML). Long term use is not recommended. It is given by
mouth.
Tioguanine or 6-thioguanine (6-TG):

6-TG

Guanine

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.

5-FU is a medication used to treat cancer. By injection into a vein it is used for colon cancer, esophageal
cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for
actinic keratosis and basal cell carcinoma.
5-Fluorouracil (5-FU):

5 FU Thymine

Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects
in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-
targeting drugs such as colchicine that inhibit microtubule assembly, paclitaxel stabilizes the
microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a
metaphase spindle configuration. This blocks the progression of mitosis and prolonged activation of
the mitotic checkpoint triggers apoptosis or reversion to the G-phase of the cell cycle without cell
division.
The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of
microtubule dynamics, but recent studies have demonstrated that suppression of dynamics occurs at
concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations,
paclitaxel appears to suppress microtubule detachment from centrosomes, a process normally
activated during mitosis. Paclitaxel binds to beta-tubulin subunits of microtubules.

Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy
medication used to treat a number of types of cancer. This includes ovarian cancer, breast
cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer. It is given by injection
into a vein. There is also an albumin bound formulation.
Taxol (Paclitaxel)
Methotrexate is an antimetabolite of the antifolate type. It is thought to affect cancer and
rheumatoid arthritis by two different pathways. For cancer, methotrexate competitively
inhibits dihydrofolate reductase (DHFR), an enzyme that participates in
the tetrahydrofolate synthesis. The affinity of methotrexate for DHFR is about 1000-fold that of
folate. DHFR catalyses the conversion of dihydrofolate to the active tetrahydrofolate. Folic acid
is needed for the de novo synthesis of the nucleoside thymidine, required for DNA synthesis.
Also, folate is essential for purine and pyrimidine base biosynthesis, so synthesis will be
inhibited. Methotrexate, therefore, inhibits the synthesis of DNA, RNA, thymidylates,
and proteins. It is used to treat cancer, autoimmune diseases, ectopic pregnancy, and for medical
abortions. Types of cancers it is used for include breast cancer, leukemia, lung cancer,
lymphoma, and osteosarcoma.

Methotrexate

Microtubule-disruptive drugs like vinblastine, Vincristine, colcemid, and nocodazole have been
reported to act by two mechanisms. At very low concentrations they suppress microtubule dynamics
and at higher concentrations they reduce microtubule polymer mass. Recent findings indicate that they
also produce microtubule fragments by stimulating microtubule minus-end detachment from their
organizing centers. Dose-response studies further indicate that enhanced microtubule detachment from
spindle poles correlate best with cytotoxicity. The uses of vinblastin includes Hodgkin's lymphoma,
non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given
by injection into a vein.
Vinca alkaloids (Vinblastine, Vincristine)

The precise mechanism of action for thalidomide is unknown, but possible mechanisms include anti-
angiogenic and oxidative stress-inducing effects. It also inhibits TNF-α, IL-6, IL-10 and IL-12
production, modulates the production of IFN-γ and enhances the production of IL-2, IL-4 and IL-5 by
immune cells. It increases lymphocyte count, costimulates T cells and modulates natural killer cell
cytotoxicity. It also inhibits NF-κB and COX-2 activity.
Thalidomide, sold under the brand name Immunoprin, among others, is an immunomodulatory drug
and the prototype of the thalidomide class of drugs. Today, thalidomide is used mainly as a treatment
of certain cancers (multiple myeloma) and of a complication of leprosy.

Vinblastine

Thanlidomide

Its mechanism of action is not fully understood. Metabolism yields azo-procarbazine and hydrogen
peroxide which results in the breaking of DNA strands.
Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain
cancers. For Hodgkin's it is often used together with mechlorethamine, vincristine, and prednisone
while for brain cancers such as glioblastoma multiforme it is used with lomustine and vincristine.

Procarbazine:

Glucocorticoids (GCs) are a class of corticosteroids, which are a class of steroid hormones.
Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor (GR), that is present in
almost every vertebrate animal cell. The name glucocorticoid (glucose + cortex + steroid) is composed
from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal
structure. GCs are part of the feedback mechanism in the immune system which reduces certain
aspects of immune function, such as reduction of inflammation. hey also interfere with some of the
abnormal mechanisms in cancer cells, so they are used in high doses to treat cancer.

Glucocorticoids:
Tamoxifen is a nonsteroidal triphenylethylene derivative that binds to the estrogen receptor. It has
both estrogenic and antiestrogenic actions, depending on the target tissue. It is strongly antiestrogenic
on mammary epithelium, hence its use in both the prevention and treatment of breast cancer; it is
proestrogenic on uterine epithelium, hence the current controversy regarding its safety in cancer
prevention.
The mechanism of action of tamoxifen is complex. Clearly, its principal mechanism of action is
mediated by its binding to the estrogen receptor and the blocking of the proliferative actions of
estrogen on mammary epithelium. One suggested mechanism for this antiproliferative action is the
induction by tamoxifen of the synthesis of the cytokine transforming growth factor-β (TGF-β), which
acts as a negative autocrine regulatory molecule.

Tamoxifen:

Flutamide
Flutamide, sold under the brand name Eulexin among others, is a synthetic, non-steroidal antiandrogen
(NSAA) used primarily to treat prostate cancer. It acts as a selective antagonist of the androgen
receptor (AR), competing with androgens such as testosterone and its powerful active metabolite
dihydrotestosterone (DHT) for binding to ARs in the prostate gland. By doing so, it prevents them
from stimulating the prostate cancer cells to grow. In addition to its use in prostate cancer, flutamide
has been used to treat hyperandrogenism (excess androgen levels) in women, such as in those with
polycystic ovary syndrome (PCOS) and hirsutism.

Topotecan:
Topotecan is a chemotherapeutic agent that is a topoisomerase-I inhibitor. It is a synthetic, water-
soluble analog of the natural chemical compound camptothecin. It is used in the form of its
hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.
Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme (which aids in DNA
unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands to break.
Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore,
this causes errors in DNA synthesis and promotes apoptosis of the cancer cell. The uses include
testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer.

Etoposide: