cancer & chronic myeloed leukemiaPresentation Transcript
Cancer is the rapid creation of abnormal
cells that grow beyond their usual
boundaries, and which can then invade
adjoining parts of the body and spread to
Human Genome Project data
• We are all 99.9% similar in our DNA.
• Individuals vary by only 0.1%
• Individual variations may correlate with
different responses to medicines and
magnitude of disease risk.
Cancer: a group of related diseases characterized by cells growing out of control.
Mutated genes that cause cancer are called oncogenes.
Tumour cells travel - metastasis
• A tumour i.e. is not capable of indefinite
growth and does not invade the healthy
surrounding tissue extensively is BENIGN.
• A tumour that continues to grow and becomes
progressively invasive is MALIGNANT.
• Malignant tumors exhibit METASTASIS.
• What makes most tumors so lethal is their ability to
metastasize -- that is, establish new tumour sites at
other locations throughout the body.
• Metastasis is now underway, as tumour cells from
the original cancer growth travel throughout the
body. Most of these cells will die soon after entering
the blood or lymph circulation.
• Metastasis ---- Cancer cells sometimes invade surrounding
tissues, often breaking through the basal laminae to establish
secondary areas of growth.
– Metastatic tumors often secrete proteases, which degrade the
surrounding extracellular matrix.
– Both primary and secondary tumors require angiogenesis, the formation
of new blood vessels, in order to grow to a large mass.
• The multi-hit model proposes that multiple mutations are needed to
To form a secondary tumour, a tumour cell needs to leave the vessel system and
invade tissue. The cell must attach itself to a vessel's wall. Once this is done, it can
work its way through the vessel and enter the tissue.
Although perhaps less than one in 10,000 tumour cells will survive long enough to
establish a new tumour site, a few survivors can escape and initiate new colonies of
Cancers as a group account for
approximately 13% of all deaths each
year with the most common being: lung
cancer (1.3 million deaths), stomach
cancer (803,000 deaths), colorectal
cancer (639,000 deaths), liver cancer
(610,000 deaths), and breast cancer
The three most common cancers
Men: Prostate, lung, and colorectal
Women: Breast, colorectal, and lung
Children: leukemia (34%), brain tumors
(23%), and lymphomas (12%).
Breast cancer is the most frequently
diagnosed cancer and the leading cause
of cancer death among
females, accounting for 23% of the total
cancer cases and 14% of the cancer
chemicals and other substances
Some viruses and bacteria
Family history of cancer
Poor diet, lack of physical activity,
There are five broad groups that are used to classify cancer.
• CARCINOMAS: cells that cover internal and external parts of the body lung, breast, and colon cancer.
• SARCOMAS: cells that are located in bone, cartilage, fat, connective
tissue, muscle, and other supportive tissues.
• LYMPHOMAS are cancers that begin in the lymph nodes and immune
• LEUKEMIA are cancers that begin in the bone marrow and often
accumulate in the bloodstream.
• ADENOMAS are cancers that arise in the thyroid, the pituitary gland, the
adrenal gland, and other glandular tissues.
Properties of cancer cells
• Lack of density dependent
growth factor production
and stimulation]. Hence no
requirement for growth
• Less adhesive than normal
cells [no contact inhibition].
• Resistant to signals that
normally program cell
Local symptoms: are restricted to the site of the primary cancer.
• lumps or swelling (tumor),
• hemorrhage ( skin, mouth or anus),
• ulceration and pain.
Metastatic symptoms: due to the spread of cancer to other locations .
• lymph nodes
• hepatomegaly or splenomegaly
• neurological symptoms.
Systemic symptoms: due to distant effects of the cancer ,not related to direct or
• weight loss (poor appetite and cachexia)
• excessive sweating (especially night sweats)
The anorexia –cachexia syndrome is typical of patients suffering from many tumor
and occurs in greater than 50% of all cancer patients and more than 85% of
pancreatic and lung cancer patients (Tisdale,2005
• 1942 - Louis Goodman and Alfred Gilman used nitrogen mustard to
• 1948 - Sydney Farber used successfully methotrexate to cure
children with acute leukemia
• 1955 - The Chemotherapy Program begins
• 1975 – A combination of cyclophosphamide, 5-fluorouracil and
methotrexate was show as an effective treatment of breast cancer
• 1978 - FDA approves cisplatin against ovarian cancer
• 1998 - FDA approves paclitaxel (Taxol), which becomes the first
oncology “blockbuster” drug
• 2001 - FDA approves imatinib (Glivec).
Beginning the era of targeted therapy
Insulin potentiation therapy
Virotherapy and Oncolytic virus
Non-invasive RF cancer treatment
Complementary and alternative treatments(CAM)
Cancer treatment depends on the type of cancer, the stage of the
age, health status, and additional personal characteristics.
It is combination of therapies and palliative care
Methods used for cancer treatment
in treatment of cancer
• Radiation therapy (radiotherapy or radiation oncology), is
the medical use of ionizing radiation as part of cancer
treatment to control malignant cells
• Radiotherapy is used for the treatment of malignant tumors
(cancer), and the primary therapy. It is also common to
combine radiotherapy with surgery, chemotherapy, hormone
therapy or some mixture of the three.
Mode of action
• Radiation therapy works by damaging the DNA of cells. The damage is
caused by a photon, electron, proton, neutron, or ion beam directly or
indirectly ionizing the atoms which make up the DNA chain. Indirect
ionization happens as a result of the ionization of water, forming free
radicals, notably hydroxyl radicals, which then damage the DNA.
• Chemotherapy, in its most general sense, refers to treatment of disease
by chemicals that kill cells, both good and bad, but specifically those of
micro-organisms or cancer.
• In the broad sense, most chemotherapeutic drugs work by impairing
mitosis (cell division), effectively targeting fast-dividing cells. As these
drugs cause damage to cells they are termed cytotoxic. Some drugs cause
cells to undergo apoptosis ( "programmed cell death").
• Antioxidants are substances that protect cells from the damage caused by
unstable molecules known as free radicals.
• Free radical damage lead to cancer.
Antioxidants interact with and stabilize free radicals and prevent damage
caused by free radicals.
• Research study in 2003 suggests that adding antioxidants to chemotherapy
can kill more cancer cells than either treatment alone when administered to
cells in laboratory(Pathak,2002)
Lipid Replacement Therapy administered as a nutritional supplement with
antioxidants can prevent oxidative membrane damage to normal
tissues, restore mitochondrial and other cellular membrane functions and
reduce the adverse effects of cancer therapy.
Recent clinical trials have shown the benefit of Lipid Replacement Therapy
plus antioxidants in restoring mitochondrial electron transport function
and other cellular membranes from oxidative damage.
• Thus dietary supplementation with antioxidants and some accessory
molecules, such as zinc and certain vitamins, are important in maintaining
antioxidant and free radical scavenging systems.
Roche Chip for Cytochrome P450
Genes: CYPC19 and CYP2D6
The world's first microarray-based
pharmacogenomic test cleared for clinical
The AmpliChip CYP450 Test provides
comprehensive detection of gene
variations — including deletions and
duplications — for the CYP2D6 and
CYP2C19 genes, which play a major role in
the metabolism of an estimated 25% of all
prescription drugs. It is intended to be an
aid to clinicians in determining therapeutic
strategy and treatment dose for
therapeutics metabolized by the CYP2D6
or CYP2C19 gene product.
Xie and Frueh, Pharmacogenomics steps toward Personalized Medicine, Personalized Medicine 2005, 2, 325-337
Field of pharmacogenetics
• First emerged around the 1950’s
• Scientists began to notice that different responses to drugs
ran in families and ethnic groups.
• Evaluates how an individual’s genetic makeup
corresponds to the response to a particular medication
• Tailors medical treatments to the individual increasing
their effectiveness while reducing side effects
• The goal of pharmacogenomics (personalised medicine) is the right
dose of drug to the patient at right time
PHARMACOGENOMICS AND CANCER
Nausea and vomiting
Gene expression: application to cancer
• Create diagnostic tests to predict
whether a patient has a genetic
predisposition to cancer
– Examine the DNA sequence of a person's
cancer-related genes to detect genetic
signatures that predict a predisposition to
– Examine a tissue sample for abnormal gene
expression patterns that indicate a
predisposition to cancer.
• Design drugs intended to treat or
– Develop drugs that inhibit the function of
proteins related to cancer.
• Design drugs to control expression of
– Drugs would interact directly with DNA in
key cells and tissues to prevent genes from
being turned on or off.
Benefits of pharmacogenetics
• New, more accurate diagnostic tests
– Predict a patient's response to specific drugs based on his or
her genetic profile.
•Personalized drug therapies
–Match a patient with effective and safe medications based on
information from diagnostic tests.
•Personalized disease prevention strategies
–Developed using genetic tests that estimate a patient's risk of
getting a particular disease, combined with personalized drug
Cancer :Preventive measures
Promoting physical activity
Healthier dietary intake