Cancer.pptx

Defining Cancer
Cancer is caused by the failure of genetic mechanisms that control the
growth and proliferation of cells.
In cancer, a single transformed cell grows to become a primary tumor,
accumulates more mutations and becomes more aggressive, then
metastasizes to another tissue and forms a secondary tumor
Cancer is a term used for diseases in which abnormal cells divide and
escape the body control.
These cells are able to:
1-Invade surrounding tissues
2-Send distant metastases.
3- Lost their functions

Tumor Characteristics
• Invade and destroy the surrounding tissue.
• The cells are genetically unstable
• Loss of normal cell architecture results in cells
that are atypical of their origin.
• Lose the ability to perform their usual functions.
• Metastasize, and consequently, recurrences are
common after removal or destruction of the
primary tumor.
• The most aggressive cancer cells display all of
these features. Alterations are caused by
mutations that affect growth factor receptors
and signal transduction genes, cell cycle
regulatory genes, DNA repair genes, or genes
controlling apoptosis. Depending on whether
the affected gene normally stimulates or inhibits
proliferation, the mutated gene is called an
oncogene or a tumor-suppressor gene.

The first step in this process is initiation, which requires
exposure of normal cells to carcinogenic substances.
Substances that may act as carcinogens or initiators
include chemical, physical, and biologic agents
Two major classes of genes are involved in
carcinogenesis: oncogenes and tumor suppressor genes
Cancer arises from the mutation of a normal gene.
Mutated genes that cause cancer are called oncogenes
Etiology of Cancer

Causes of Cancer
Genetic predisposition-
– Rb, p53, APC, CDKN2A, BRCA1, BRCA2
Infectious agents
– Viral
 HPV – cervical cancer
 Hepatitis – liver cancer
 EBV - Lymphoma
–Bacterial
 H. pylori – stomach cancer

Types of genes linked to cancer
Many of the genes that contribute to cancer development fall into broad
categories:
Tumor suppressor genes: These are protective genes. Normally, they limit cell
growth by:
-Monitoring how quickly cells divide into new cells
-Repairing mismatched DNA
-Controlling when a cell dies
When a tumor suppressor gene mutates, cells grow uncontrollably. And they may
eventually form a tumor.
Examples of tumor suppressor genes include, BRCA1, BRCA2 and p53 or TP53.
Germline mutations in BRCA1 or BRCA2 genes increase a woman’s risk of
developing hereditary breast or ovarian cancers and a man’s risk of developing
hereditary prostate or breast cancers. They also increase the risk of pancreatic
cancer and melanoma in women and men.
The most commonly mutated gene in people with cancer is p53 or TP53. More than
50% of cancers involve a missing or damaged p53 gene. Most p53 gene mutations
are acquired. Germline p53 mutations are rare, but patients who carry them are at
a higher risk of developing many different types of cancer.

Types of genes linked to cancer
Oncogenes. These turn a healthy cell into a cancerous cell. Mutations in these genes are not
known to be inherited.
Two common oncogenes are:
HER2, a specialized protein that controls cancer growth and spread. It is found in some cancer
cells. For example, breast and ovarian cancer cells.
The RAS family of genes, which makes proteins involved in cell communication pathways, cell
growth, and cell death.
DNA repair genes. These fix mistakes made when DNA is copied. Many of them function as
tumor suppressor genes.
• BRCA1,
• BRCA2, and
• p53 are all DNA repair genes.
If a person has an error in a DNA repair gene, mistakes remain uncorrected. Then, the mistakes
become mutations. These mutations mayeventually lead to cancer, particularly mutations in
tumor suppressor genes or oncogenes. Mutations in DNA repair genes may be inherited or
acquired. Lynch syndrome is an example of the inherited kind.
• BRCA1,
• BRCA2, and
• p53 mutations and their associated syndromes are also inherited.

Different Treatment Modalities
• Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy,
targeted therapy (including immunotherapy such as monoclonal antibody therapy) and
synthetic lethality, most commonly as a series of separate treatments (e.g. chemotherapy
before surgery). The choice of therapy depends upon the location and grade of the tumor
and the stage of the disease, as well as the general state of the patient (performance status).
• systemic therapy (drug therapy - cytotoxic agents, hormones, biologics) distributes widely
through the body - normal and malignant tissues
• local therapy (surgery, radiation) is directed to a defined area of documented or presumed
disease

Types of Chemo Drugs
Chemo drugs can be grouped by how they work, their chemical structure, and their
relationships to other drugs. Some drugs work in more than one way and may belong to
more than one group.
Alkylating agents
Alkylating agents keep the cell from reproducing (making copies of itself) by damaging its
DNA. These drugs work in all phases of the cell cycle and are used to treat many different
cancers, including cancers of the lung, breast, and ovary as well as leukemia, lymphoma,
Hodgkin disease, multiple myeloma, and sarcoma.
Because these drugs damage DNA, they can affect the cells of the bone marrow which
make new blood cells. In rare cases, this can lead to leukemia. The risk of leukemia from
alkylating agents is “dose-dependent,” meaning that the risk is small with lower doses but
goes up as the total amount of the drug used gets higher. The risk of leukemia after getting
alkylating agents is highest about 5 to 10 years after treatment.
Examples of alkylating agents include:
Altretamine, Bendamustine, Busulfan, Carboplatin, Carmustine, Chlorambucil, Cisplatin,
Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan,
Oxaliplatin, Temozolomide, Thiotepa, Trabectedin

Nitrosoureas
Nitrosoureas are a group of alkylating agents that have a special action.
The other alkylating agents listed above cannot travel into the brain,
but nitrosoureas are able to do so. They can enter the brain because
they are able to cross through the area known as the blood-brain
barrier, a special area that keeps most drugs out of the brain. This
action makes these drugs useful in treating certain types of brain
tumors.
Examples of nitrosoureas include:
• Carmustine
• Lomustine
• Streptozocin

Antimetabolites
Antimetabolites interfere with DNA and RNA by acting as a substitute for
the normal building blocks of RNA and DNA. When this happens, the
DNA cannot make copies of itself, and a cell cannot reproduce. They are
commonly used to treat leukemias, cancers of the breast, ovary, and the
intestinal tract, as well as other types of cancer.
Examples of antimetabolites include: Azacitidine, 5-fluorouracil (5-FU),
6-mercaptopurine (6-MP), Capecitabine (Xeloda), Cladribine,
Clofarabine, Cytarabine (Ara-C), Decitabine, Floxuridine, Fludarabine,
Gemcitabine (Gemzar), Hydroxyurea, Methotrexate, Nelarabine,
Pemetrexed (Alimta), Pentostatin, Pralatrexate, Thioguanine,
Trifluridine/tipiracil combination

Anti-tumor antibiotics
These drugs are not like the antibiotics used to treat infections. They work by changing the DNA
inside cancer cells to keep them from growing and multiplying.
Anthracyclines: Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in
copying DNA during the cell cycle. They bind with DNA so it cannot make copies of itself, and a cell
cannot reproduce. (Enzymes are proteins that start, help, or speed up the rate of chemical reactions
in cells.) They are widely used for a variety of cancers.
Examples of anthracyclines include: Daunorubicin, Doxorubicin (Adriamycin), Doxorubicin liposomal,
Epirubicin, Idarubicin, Valrubicin
A major concern when giving these drugs is that they can permanently damage the heart if given in
high doses. For this reason, lifetime dose limits (also called cumulative dose) are often placed on
these drugs.
Anti-tumor antibiotics that are not anthracyclines include: Bleomycin, Dactinomycin, Mitomycin-C,
Mitoxantrone (also acts as a topoisomerase II inhibitor)
Topoisomerase inhibitors
These drugs are also called plant alkaloids. They interfere with enzymes called topoisomerases, which
help separate the strands of DNA so they can be copied. (Enzymes are proteins that cause chemical
reactions in living cells.) Topoisomerase inhibitors are used to treat certain leukemias, as well as lung,
ovarian, gastrointestinal, colorectal, and pancreatic cancers.
Topoisomerase inhibitors are grouped according to which type of enzyme they affect:
Topoisomerase I inhibitors (also called camptothecins) include: Irinotecan, Irinotecan liposomal,
Topotecan, Topoisomerase II inhibitors (also called epipodophyllotoxins) include: Etoposide (VP-16),
Mitoxantrone (also acts as an anti-tumor antibiotic), Teniposide, Topoisomerase II inhibitors can
increase the risk of a second cancer.

Mitotic inhibitors
Mitotic inhibitors are also called plant alkaloids. They are compounds
derived from natural products, such as plants. They work by stopping
cells from dividing to form new cells, but can damage cells in all phases
by keeping enzymes from making proteins needed for cell reproduction.
Examples of mitotic inhibitors include the taxanes and vinca alkaloids.
Taxanes include- Cabazitaxel, Docetaxel, Nab-paclitaxel, Paclitaxel
Vinca alkaloids include- Vinblastine, Vincristine, Vincristine liposomal,
Vinorelbine
They are used to treat many different types of cancer including breast,
lung, myelomas, lymphomas, and leukemias. These drugs may cause
nerve damage, which can limit the amount that can be given.

Corticosteroids:
Corticosteroids, often simply called steroids, are natural hormones and
hormone-like drugs that are useful in the treatment of many types of
cancer, as well as other illnesses. When these drugs are used as part of
cancer treatment, they are considered chemotherapy drugs.
Examples of corticosteroids include:
Prednisone, Methylprednisolone, Dexamethasone
Steroids are also commonly used to help prevent nausea and vomiting
caused by chemo. They are used before some types of chemo to help
prevent severe allergic reactions, too.

Other chemotherapy drugs
Some chemotherapy drugs act in slightly different ways and do
not fit well into any of the other categories. Here are some
examples:
• All-trans-retinoic acid
• Arsenic trioxide
• Asparaginase
• Eribulin
• Hydroxyurea
• Ixabepilone
• Mitotane
• Omacetaxine
• Pegaspargase
• Procarbazine
• Romidepsin
• Vorinostat

Hormonal Therapy
 Hormonal therapy is a treatment that uses medicines o block or lower
the amount of hormones in the body to slow down or stop the
growth of cancer.
 It involves the manipulation of the endocrine system through
exogenous or external administration of specific hormones,
particularly steroid hormones, or drugs which inhibit the production
or activity of such hormones (hormone antagonists). Because steroid
hormones are powerful drivers of gene expression in certain cancer
cells, changing the levels or activity of certain hormones can cause
certain cancers to cease growing, or even undergo cell death.
 Surgical removal of endocrine organs, such as orchiectomy and
oophorectomy can also be employed as a form of hormonal therapy.

• Breast cancer hormone therapy
• The female hormones oestrogen and progesterone affect some
breast cancers. Doctors describe these cancers as oestrogen receptor
positive (ER+) or progesterone receptor positive (PR+) or both.
Hormone treatment for breast cancer works by stopping these
hormones getting to the breast cancer cells.
• Tamoxifen
• Tamoxifen works by blocking the oestrogen receptors. It stops
oestrogen from telling the cancer cells to grow.
• Tamoxifen is one of most common hormone therapies for breast
cancer. Women who are still having periods (are pre menopausal) and
women who have had their menopause (are post menopausal)
can take tamoxifen.
• Hormone therapy (tamoxifen or raloxifene) might be offered to
people at high risk of breast cancer. This is called chemoprevention.
This is not suitable for everyone.

• Aromatase Inhibitors
• You might have an aromatase inhibitor if you have been through the
menopause.
• After menopause, your ovaries stop producing oestrogen. But your
body still makes a small amount by changing other hormones (called
androgens) into oestrogen. Aromatase is the enzyme that makes this
change happen. Aromatase inhibitors block aromatase so that it can’t
change androgens into oestrogen.
• There are a few different types of aromatase inhibitor. We have
detailed information about aromatase inhibitors, including
anastrozole (Arimidex), exemestane (Aromasin) and letrozole
(Femara).

• Luteinising hormone releasing hormone (LHRH) agonists or LH
blockers
• A gland in the brain called the pituitary gland produces luteinising
hormone (LH) which controls the amount of hormones made by the
ovaries.
• LH blockers are drugs that stop the production of luteinising hormone.
They do this by blocking the signal from the pituitary gland to the
ovaries. So, the ovaries stop making oestrogen or progesterone.
• You will only have this treatment if you have not had your menopause
yet. After menopause, your ovaries don’t produce hormones, so this
type of drug won’t help.
• One type used for breast cancer is goserelin (Zoladex).
• Fulvestrant
• Fulvestrant (Faslodex) stops oestrogen getting to the cancer cells by
blocking oestrogen receptors and reducing the number of receptors
the cancer cells have. You might have this in combination with other
cancer drugs.

• Prostate cancer hormone therapy
• Prostate cancer depends on testosterone to grow. Hormone therapy blocks
or lowers the amount of testosterone in the body.
• This can lower the risk of an early prostate cancer coming back when you
have it with other treatments. Or, it can shrink an advanced prostate cancer
or slow its growth.
Luteinising hormone releasing hormone (LHRH) agonists or LH blockers
• A gland in the brain called the pituitary gland produces luteinising hormone
(LH). This controls the amount of testosterone made by the testicles.
• LH blockers are drugs that stop the production of luteinising hormone. They
do this by blocking the signal from the pituitary gland to the testicles. So the
testicles stop making testosterone.
• Types for prostate cancer include goserelin (Zoladex), leuprorelin (Prostap)
and triptorelin (Decapetyl).
Anti androgens
• Prostate cancer cells have areas called receptors. Testosterone attaches to
these receptors and that can encourage the cells to divide so that the cancer
grows.
• Anti androgen drugs work by attaching themselves to these receptors. This
stops testosterone from reaching the prostate cancer cells.
• There are different types of anti androgens including bicalutamide (Casodex),
cyproterone acetate (Cyprostat) and flutamide (Drogenil).

• Prostate cancer hormone therapy
Gonadotrophin releasing hormone (GnRH) blocker
• Gonadotrophin releasing hormone (GnRH) blockers stop messages
from a part of the brain called the hypothalamus that tell the
pituitary gland to produce luteinising hormone.
• Luteinising hormone tells the testicles to produce testosterone. So,
blocking GnRH stops the testicles producing testosterone. The drug
degarelix (Firmagon) is a GnRH blocker.
Other hormone therapies
• There are other newer hormonal treatments for prostate cancer.
These therapies include:
• enzalutamide
• abiraterone
• darolutamide

• Womb/uterus cancer hormone therapy
The female hormones oestrogen and progesterone affect the growth
and activity of the cells that line the womb. Doctors use progesterone
treatment to help shrink larger womb cancers or to treat womb
cancers that have come back.
There are different types of progesterone that you might have
including medroxyprogesterone acetate (Provera) and megestrol
(Megace).

Immunotherapy
A type of therapy that uses substances to stimulate or suppress the
immune system to help the body fight cancer, infection, and other
diseases. Some types of immunotherapy only target certain cells of the
immune system. Others affect the immune system in a general way.
Types of immunotherapy include cytokines, vaccines, bacillus
Calmette-Guerin (BCG), and some monoclonal antibodies.

Types of immunotherapy
• monoclonal antibodies
• checkpoint inhibitors
• vaccines
• cytokines
• CAR-T cell therapy.

Monoclonal Antibodies (MAB)
• Antibodies are found naturally in our blood and
help us to fight infection. MAB therapies mimic
natural antibodies but are made in a laboratory.
Monoclonal just means all one type. So each
MAB is a lot of copies of one type of antibody.
• A MAB works by recognising and finding specific
proteins on cells. Some work on cancer cells,
others target proteins on cells of the immune
system.
• Each MAB recognises one particular protein.
They work in different ways depending on the
protein they are targeting.
• MABs work as an immunotherapy in different
ways. Some MABs work in more than one way.
They can:
• trigger the immune system to attack and kill
cancer cells
• act on cells to help the immune system attack
cancer cells

MAB
• Some MABs trigger the immune system to attack and kill cancer cells
• Some MABs attach themselves to cancer cells, making it easier for the cells
of the immune system to find them. This process is called antibody-
dependent cell-mediated cytotoxicity or ADCC.
• Monoclonal antibodies (MABs) which trigger the immune system to treat
cancer
-An injected monoclonal antibody seeks out cancer cell proteins.
-The monoclonal antibody bind to the proteins.
-The antibodies signal to immune cells.
-The immune cells arrive and punch holes in the cancer cell. The cancer cell
dies.
Examples of MABS that work in this way include:
• rituximab (Mabthera) – a treatment for chronic lymphocytic leukaemia (CLL)
and some types of non Hodgkin lymphoma
• cetuximab (Erbitux) – a treatment for advanced bowel cancer and head and
neck cancer
• trastuzumab (Herceptin) – used to treat breast cancer and stomach cancer

Checkpoint Inhibitors
Other MABs work by acting on cells of the immune system. For example, a
type of immunotherapy called checkpoint inhibitors. Checkpoint inhibitors
block proteins that stop the immune system attacking cancer cells.
Checkpoint inhibitors block different proteins, including:
• CTLA-4 (cytotoxic T lymphocyte associated protein 4): Ipilumab
• PD-1 (programmed cell death protein 1)
• PD-L1 (programmed death ligand 1)
So you might hear these drugs named after these checkpoint proteins – for
example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors.
Examples of checkpoint inhibitors include:
• CTLA-4 inhibitors: Ipilimumab (Yervoy)
• PD-1 inhibitors: nivolumab (Opdivo), pembrolizumab (Keytruda)
• PD-L1 inhibitors: atezolizumab, avelumab, durvalumab
Nivolumab and pembrolizumab are used to treat several different types of
cancer.

Checkpoint Inhibitors
• T cells have proteins on them that turn on an immune response and other
proteins that turn it off. These are called checkpoint proteins.
• Some checkpoint proteins help tell T cells to become active, for example
when an infection is present. But if T cells are active for too long, or react to
things they shouldn’t, they can start to destroy healthy cells and tissues. So
other checkpoints help tell T cells to switch off.
• Some cancer cells make high levels of proteins. These can switch off T cells,
when they should really be attacking the cancer cells. So the cancer cells are
pushing a stop button on the immune system. And the T cells can no longer
recognise and kill cancer cells.
• Drugs that block checkpoint proteins are called checkpoint inhibitors. They
stop the proteins on the cancer cells from pushing the stop button. This
turns the immune system back on and the T cells are able to find and attack
the cancer cells.

Cytokines
Cytokines are a group of proteins in the body that play an important part
in boosting the immune system. Interferon and interleukin are types of
cytokines found in the body. Scientists have developed man made
versions of these to treat cancer.
The man made version of interleukin is called aldesleukin
Interferon and aldesleukin work in several ways, including:
• interfering with the way cancer cells grow and multiply
• stimulating the immune system and encouraging killer T cells and
other cells to attack cancer cells
• encouraging cancer cells to produce chemicals that attract immune
system cells to them

Targeted Therapy
A type of treatment that uses drugs or other substances to identify and
attack specific types of cancer cells with less harm to normal cells.
Some targeted therapies block the action of certain enzymes, proteins,
or other molecules involved in the growth and spread of cancer cells.
Other types of targeted therapies help the immune system kill cancer
cells or deliver toxic substances directly to cancer cells and kill them.
Targeted therapy may have fewer side effects than other types of
cancer treatment. Most targeted therapies are either small molecule
drugs or monoclonal antibodies.

Targeted Therapy
• As a form of molecular medicine, targeted therapy blocks the growth
of cancer cells by interfering with specific targeted molecules needed
for carcinogenesis and tumor growth.
• Because most agents for targeted therapy are biopharmaceuticals,
the term biologic therapy is sometimes synonymous with targeted
therapy when used in the context of cancer therapy (and thus
distinguished from chemotherapy, that is, cytotoxic therapy).
However, the modalities can be combined; antibody-drug conjugates
combine biologic and cytotoxic mechanisms into one targeted
therapy.
• Many targeted therapies are examples of immunotherapy (using
immune mechanisms for therapeutic goals) developed by the field of
cancer immunology. Thus, as immunomodulators, they are one type
of biological response modifiers.
• The main categories of targeted therapy are currently small
molecules and monoclonal antibodies.

Types of Targeted Therapy
• There are many different types of targeted cancer drugs. These are
grouped together depending on how they work. Some drugs belong
to more than one group because they work in more than one way.
For example, a drug that works by blocking cancer cell growth may
also be a monoclonal antibody.
• Some of these targeted drugs might also be called immunotherapies
or biological therapies.
• monoclonal antibodies
• cancer growth blockers
• drugs that block cancer blood vessel growth
• PARP inhibitors

MAB
• MABs work in different ways and some work in more than one way. They may do
one of the following:
• Block signals telling cancer cells to divide: Cancer cells often make large
amounts of molecules called growth factor receptors. These sit on the cell
surface and send signals to help the cell survive and divide. Some MABs stop
growth factor receptors from working properly, either by blocking the signal or
the receptor itself. So the cancer cell no longer receives the signals it needs.
• Carry cancer drugs or radiation to cancer cells: Some MABs have drugs or
radioactive substances attached to them. The MAB finds the cancer cells and
delivers the drug or radioactive substance directly to them. These are called
conjugated MABs.
• Help your immune system find and kill cancer cells: Some MABS have an effect
on the immune system. The immune system is then in a better position to kill
cancer cells. Because MABs work in different ways, some of these drugs are also
a type of immunotherapy. They do this by blocking proteins that stop the
immune system working (checkpoint inhibitors) or attaching to cancer cells,
making it easier for the cells of the immune system to find them (a process called
antibody-dependent cell-mediated cytotoxicity, or ADCC)
• Block signals telling cancer cells to develop a blood supply (anti angiogenic
drugs): Some cancer cells make a protein called vascular endothelial growth
factor (VEGF). The VEGF protein attaches to receptors on cells that line the walls
of blood vessels within the tumour. This triggers the blood vessels to grow so the
cancer can then grow. Some MABs block vascular endothelial growth factor
(VEGF) from attaching to the receptors on the cells that line the blood vessels.
These MABs are called anti angiogenic drugs.

Cancer Growth Blockers
• Growth factors are chemicals produced by the body that control cell
growth. There are many different types of growth factors and they all
work in different ways.
• Growth factors work by binding to receptors on the cell surface. This
sends a signal to the inside of the cell, which sets off a chain of
complicated chemical reactions.
• There are a number of different growth factors. These include:
• epidermal growth factor (EGF) – controls cell growth
• vascular endothelial growth factor (VEGF) – controls blood vessel
development
• platelet derived endothelial growth factor (PDGF) – controls blood vessel
development and cell growth
• fibroblast growth factor (FGF) – controls cell growth
• Each growth factor works by attaching to the corresponding receptor
on the cell surface. For example, EGF binds to epidermal growth
factor receptor (EGFR).

• A cancer growth blocker is a targeted drug that blocks the growth
factors that trigger cancer cells to divide and grow. Scientists are
looking at different ways of doing this such as:
• lowering levels of the growth factor in the body
• blocking the growth factor receptor on the cancer cell
• blocking the signals inside the cell that start up when the growth factor
triggers the receptor
• Most of these treatments work by blocking the signalling processes
that cancer cells use to divide.
• Cancer cells are often very sensitive to growth factors. So if we can
block them, we can stop some types of cancer from growing and
dividing. Scientists are developing different inhibitors for the different
types of growth factors.

Types of cancer growth blockers
Tyrosine kinase inhibitors
Tyrosine kinase inhibitors (TKIs) block chemical messengers (enzymes)
called tyrosine kinases. Tyrosine kinases help to send growth signals in
cells, so blocking them stops the cell growing and dividing.
Cancer growth blockers can block one type of tyrosine kinase or more
than one type. TKIs that block more than one type of tyrosine kinase are
called multi TKIs.
Examples of TKIs include:
•axitinib (Inlyta)
•dasatinib (Sprycel)
•erlotinib (Tarceva)
•imatinib (Glivec)
•nilotinib (Tasigna)
•pazopanib (Votrient)
•sunitinib (Sutent)

• Tyrosine Kinases are chemical messengers (enzymes) used by cells to
control how they grow and divide. They act like an ‘on-off’
switch. When the growth factor attaches to the outside of the cell it
switches the tyrosine kinase ‘on’. This signals the cell to divide.

• Proteasome inhibitors
• Proteasomes are tiny, barrel shaped structures found in all
cells. They help break down proteins the cell doesn't need
into smaller parts. The cell can then use them to make new
proteins that it does need.
• Drug treatments that block proteasomes from working are
called proteasome inhibitors. They cause a build up of
unwanted proteins in the cell, which makes the cancer cells
die.
• Doctors use proteasome inhibitors to treat myeloma.
Examples include:
• bortezomib (Velcade)
• carfilzomib (Kyprolis)
• ixazomib (Ninlaro)

• mTOR inhibitors
• mTOR(Mammalian target of rapamycin) is a type of protein called a
kinase protein. It can make cells produce chemicals (such as cyclins) that
trigger cell growth. It may also make cells produce proteins that trigger
the development of new blood vessels. Cancers need new blood vessels
in order to grow.
• In some types of cancer mTOR is switched on, which makes the cancer
cells grow and produce new blood vessels. mTOR blockers (inhibitors)
can stop the growth of some types of cancer.
• mTOR inhibitors include:
• temsirolimus (Torisel)
• everolimus (Afinitor)

• PI3K inhibitors
• PI3Ks are a group of closely related kinase proteins. Their full name
is phospho inositide 3 kinases.
• They do a number of different things in cells. For example, they act like
switches in the cell turning on other proteins such as mTOR
• Switching on PI3Ks might make cells grow and multiply, or trigger the
development of blood vessels, or help cells to move around.
• In some cancers PI3K is permanently switched on, which means that the
cancer cells grow uncontrollably. Researchers have been developing new
treatments that inhibit PI3K.
• For example, idelalisib (Zydelig) is now available as a treatment for some
people with chronic lymphocytic leukaemia (CLL).

• Histone deacetylase inhibitors
• Histone deacetylase inhibitors are also called HDAC inhibitors or HDIs.
• They block the action of a group of enzymes that remove chemicals
called acetyl groups from particular proteins. This can stop the cancer
cell from using some genes that would help it to grow and divide.
This might kill the cancer cell completely.
• HDACs are a newer type of cancer growth blocker. Panobinostat is an
example of an HDAC. It is a treatment for myeloma. Researchers are
looking at some other HDACs including:
• vorinostat
• romidepsin

• Hedgehog pathway blockers
• Hedgehog pathway blockers are drugs that target a group of proteins
known as the hedgehog pathway. In the developing embryo, these
proteins send signals that help cells to grow in the right place and in the
right way.
• The hedgehog pathway can also control the growth of blood vessels and
nerves. In adults, hedgehog pathway proteins are not usually active. But
in some people, changes in a gene switch them on. Hedgehog pathway
blockers are designed to switch off the proteins and stop the growth of
the cancer.
• Vismodegib (Erivedge) is an example of a hedgehog pathway blocker. It is
used in some situations to treat people with basal cell skin cancer that
has spread.

• BRAF and MEK inhibitors
• BRAF inhibitors directly block a protein called BRAF. BRAF is a chemical messenger (enzyme)
that controls how cells grow and send signals.
• Some cancers have a change (mutation) in the BRAF gene. This genetic change makes the
cancer cells produce too much BRAF protein, which can make cancer cells grow. BRAF
inhibitors block the BRAF proteins and can stop cancer cells growing.
• BRAF inhibitors are a treatment for advanced melanoma. Examples include:
• vemurafenib (Zelboraf)
• dabrafenib (Tafinlar)
• encorafenib (Braftovi)
• The BRAF protein can affect other proteins, such as MEK, which makes cancer cells divide and
grow in an uncontrolled way. MEK inhibitors are another type of targeted cancer drug. They
work by blocking the MEK protein, which slows down the growth of cancer cells. Two MEK
inhibitors for melanoma are:
• trametinib (Mekinist)
• binimetinib (Mektovi)
• You usually have a BRAF inhibitor with a MEK inhibitor. This is because having the combination
of both drugs can work better.

Drugs that block cancer blood vessel growth
(anti angiogenics)
• Angiogenesis means the growth of new blood vessels. So anti
angiogenic drugs are treatments that stop tumours from growing
their own blood vessels. If the drug is able to stop a cancer from
growing blood vessels, it might slow the growth of the cancer or
sometimes shrink it.
• Some cancer cells make a protein called vascular endothelial growth
factor (VEGF). The VEGF protein attaches to receptors on cells that
line the walls of blood vessels within the tumour. The cells are called
endothelial cells. This triggers the blood vessels to grow so the
cancer can then grow.

Types of anti angiogenesis treatment
• Drugs that block blood vessel growth factor
• Some drugs block vascular endothelial growth factor (VEGF) from
attaching to the receptors on the cells that line the blood vessels.
This stops the blood vessels from growing.
• An example of a drug that blocks VEGF is bevacizumab (Avastin).
Bevacizumab is also a monoclonal antibody. It is a treatment for
several different types of cancer. Other examples include:
• aflibercept
• ramucirumab

• Drugs that block signalling within the cell
• Some drugs stop the VEGF receptors from sending growth signals
into the blood vessel cells. These treatments are also called cancer
growth blockers or tyrosine kinase inhibitors (TKIs).
• Examples of TKIs that block signals inside blood vessels cells include:
• sunitinib
• sorafenib
• axitinib
• regorafenib
• cabozantinib

• Drugs that affect signals between cells
• Some drugs act on the chemicals that cells use to signal to each other
to grow. This can block the formation of blood vessels.
• Drugs that works in this way include thalidomide and lenalidomide
(Revlimid). They are used to treat some people with multiple
myeloma.

PARP inhibitors
• PARP is a protein (enzyme) found in our cells, it stands for poly-ADP
ribose polymerase. It helps damaged cells to repair themselves.
• As a cancer treatment, PARP inhibitors stop the PARP from doing its
repair work in cancer cells and the cell dies.
• Researchers first looked at these drugs in cancers that already had
problems repairing cell damage. They focused on cancers with a
change (or fault) in genes called BRCA.
• Normally, BRCA1 and BRCA2 genes play a part in cell repair in the
body. Cells are less likely to repair themselves if there is a fault in one
or both of these genes. People who have faulty BRCA genes have an
increased risk of certain cancers including:
• breast cancer
• ovarian cancer
• prostate cancer
• Cancer cells with BRCA gene faults already have a poor repair system.
So blocking PARP with a PARP inhibitor drug means that the cells are
not able to repair themselves and they die.

PARP inhibitors
• PARP inhibitors are a treatment for the following types of cancer:
• ovarian cancer
• fallopian tube cancer
• peritoneal cancer
• Researchers think that they might work in cancers that have
weaknesses in the cell similar to the BRCA gene fault. There are trials
to find whether they are useful in other types of cancer including:
• lung cancer
• pancreatic cancer
• head and neck cancer
• a type of brain tumour called glioblastoma multiforme
• prostate cancer
• cancer of the stomach and foodpipe (oesophagus)
• womb and cervical cancer
• kidney and bladder cancer

Types of PARP inhibitors
•There are different types of PARP inhibitors
including:
• olaparib (Lynparza)
• rucaparib (Rubraca)
• niraparib (Zejula)
•These PARP inhibitors are for some women with
one of the following types of cancer:
• ovarian cancer
• fallopian tube cancer
• peritoneal cancer

Small Molecules
Many are tyrosine-kinase inhibitors.
• Imatinib (Gleevec, also known as STI–571) is approved for chronic myelogenous
leukemia, gastrointestinal stromal tumor and some other types of cancer. Early clinical
trials indicate that imatinib may be effective in treatment of dermatofibrosarcoma
protuberans.
• Gefitinib (Iressa, also known as ZD1839), targets the epidermal growth factor receptor
(EGFR) tyrosine kinase and is approved in the U.S. for non small cell lung cancer.
• Erlotinib (marketed as Tarceva). Erlotinib inhibits epidermal growth factor receptor,
and works through a similar mechanism as gefitinib. Erlotinib has been shown to
increase survival in metastatic non small cell lung cancer when used as second line
therapy. Because of this finding, erlotinib has replaced gefitinib in this setting.
• Sorafenib (Nexavar), Sunitinib (Sutent), Dasatinib (Sprycel), Lapatinib (Tykerb),
Nilotinib (Tasigna)
• Bortezomib (Velcade) is an apoptosis-inducing proteasome inhibitor drug that causes
cancer cells to undergo cell death by interfering with proteins. It is approved in the
U.S. to treat multiple myeloma that has not responded to other treatments.

• The selective estrogen receptor modulator tamoxifen has been described as
the foundation of targeted therapy.
• Janus kinase inhibitors, e.g. FDA approved tofacitinib
• ALK inhibitors, e.g. crizotinib
• Bcl-2 inhibitors (e.g. FDA approved venetoclax, obatoclax in clinical trials,
navitoclax, and gossypol.
• PARP inhibitors (e.g. FDA approved olaparib, rucaparib, niraparib and
talazoparib)
• PI3K inhibitors (e.g. perifosine in a phase III trial)
• Apatinib is a selective VEGF Receptor 2 inhibitor which has shown encouraging
anti-tumor activity in a broad range of malignancies in clinical trials.
• Apatinib is currently in clinical development for metastatic gastric carcinoma,
metastatic breast cancer and advanced hepatocellular carcinoma.
• Zoptarelin doxorubicin (AN-152), doxorubicin linked to [D-Lys(6)]- LHRH, Phase
II results for ovarian cancer.
Small Molecules

• Braf inhibitors (vemurafenib, dabrafenib, LGX818) used to treat metastatic melanoma
that harbors BRAF V600E mutation
• MEK inhibitors (trametinib, MEK162) are used in experiments, often in combination
with BRAF inhibitors to treat melanoma
• CDK inhibitors, e.g. PD-0332991, LEE011 in clinical trials
• Hsp90 inhibitors, some in clinical trials
• Hedgehog pathway inhibitors (e.g. FDA approved vismodegib and sonidegib).
• salinomycin has demonstrated potency in killing cancer stem cells in both laboratory-
created and naturally occurring breast tumors in mice.
• VAL-083 (dianhydrogalactitol), a “first-in-class” DNA-targeting agent with a unique bi-
functional DNA cross-linking mechanism. NCI-sponsored clinical trials have
demonstrated clinical activity against a number of different cancers including
glioblastoma, ovarian cancer, and lung cancer. VAL-083 is currently undergoing Phase 2
and Phase 3 clinical trials as a potential treatment for glioblastoma (GBM) and ovarian
cancer. As of July 2017, four different trials of VAL-083 are registered.
Small Molecules

Serine/threonine kinase inhibitors (small molecules)
• Vintafolide is a small molecule drug conjugate consisting of a small
molecule targeting the folate receptor. It is currently in clinical trials
for platinum-resistant ovarian cancer (PROCEED trial) and a Phase 2b
study (TARGET trial) in non-small-cell lung carcinoma (NSCLC).
Small molecule drug conjugates
• Temsirolimus (Torisel)
• Everolimus (Afinitor)
• Vemurafenib (Zelboraf)
• Trametinib (Mekinist)
• Dabrafenib (Tafinlar)

Monoclonal antibodies
Examples of licensed monoclonal antibodies include:
• Pembrolizumab (Keytruda) binds to PD-1 proteins found on T cells.
Pembrolizumab blocks PD-1 and help the immune system kill cancer cells. It is
used to treat melanoma, Hodgkin's lymphoma, non-small cell lung carcinoma and
several other types of cancer.
• Rituximab targets CD20 found on B cells. It is used in non Hodgkin lymphoma
• Trastuzumab targets the Her2/neu (also known as ErbB2) receptor expressed in
some types of breast cancer
• Alemtuzumab
• Cetuximab target the epidermal growth factor receptor (EGFR). It is approved for
use in the treatment of metastatic colorectal cancer and squamous cell carcinoma
of the head and neck.
• Panitumumab also targets the EGFR. It is approved for the use in the treatment of
metastatic colorectal cancer.
• Bevacizumab targets circulating VEGF ligand. It is approved for use in the
treatment of colon cancer, breast cancer, non-small cell lung cancer, and is
investigational in the treatment of sarcoma. Its use for the treatment of brain
tumors has been recommended.
• Ipilimumab (Yervoy)
• Many antibody-drug conjugates (ADCs) are being developed and also ADEPT
(antibody-directed enzyme prodrug therapy).

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