cancer

• Cancer is one of the most common diseases in the developed world:

• 1 in 4 deaths are due to cancer

• 1 in 17 deaths are due to lung cancer

• Lung cancer is the most common cancer in men

• Breast cancer is the most common cancer in women

• There are over 100 different forms of cancer

• Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells.

• Cancer is caused by external factors and internal factors which may act together to initiate or promote carcinogenesis.

– External Factors – chemicals, radiation, viruses, and lifestyle

– internal Factors – hormones, immune condition, and inherited mutations

Factors Believed to Contribute to Global Causes of Cancer

Cancer prevention?

• Cancer prevention is defined as active measures to decrease the risk of cancer.

• Cancer is considered as the largely preventable disease.

• Prevention offers the most cost-effective long-term strategy for the control of cancer as 30-40% of cancers can be prevented, and one-third of cancers can be cured through early diagnosis and treatment.

Preventable risk factors

• Tobacco

• Obesity

• Physical inactivity

• Alcohol

• Sun exposure

• Infections

• Pollution

STRATEGIES FOR CANCER PREVENTION

ANDMANAGEMENT

What Is Chemoprevention?

• The science of trying to apply natural and synthetic compounds to interfere with the earliest stages of carcinogenesis, before

invasive cancer appears

The Ideal Chemo preventive

Agent

• Is effective

• Easily administered

• Preferably once/twice day

• Little or ideally no toxicity

• Affordable

Mechanisms of Chemoprevention

• Antioxidants: defense against radicals

• Anti-proliferative agents

• Anti-hormonal compounds

• Disruption of mutational gain or loss of function

Strategy#1-dietary strategy for cancer prevention

• 30% to 40% of all cancers may be prevented by changes in diet and physical activity.

• Increase antioxidants by eating a variety of anti-oxidant rich fruits and vegetables including nuts, seeds , herbs and spices.

• Antioxidants supplements mainly contain:-1.Vitamin a,c,e,d and k2.alpha-lipoic acid3.co-enzyme q104. Falvanoids from plants including lycopene, resveratrol and quercetin.5. Carotenoids6.selenium

Foods that contain antioxidants:

• VITAMIN A- CARROTS, SWEET POTATOES, MEAT• VITAMINC- CHERRIES, PEPPERS, BERRIES,

CABBAGE, BROCOLI, CITRUS • VITAMIN E-WALNUTS, SESAME SEEDS• VITAMIN D- COD LIVER OIL, SALMON, EGGS,

FORTIFIED FOODS• VITAMIN K-CAULIFLOWER, SPROUTS, BEANS• SELENIUM-INCLUDES SEAFOODS• ALPHA LIPOIC ACID-SPINACH, BROCOLI• CO-ENXYME Q10-MEAT, SEAFOOD

FLAVONOIDS

• CLASS OF PLANT SECONDARY METABOLOITIES

• HAVE ANTIOXIDANTL ACTIVITY

• Knowns as vitamin p

• Found in fruits and vegetables

classification

• Flavonols- compounds:- quercetin , kaempferol (e.g- cherry tomato, apple, blueberry)

• Flavones-compounds:- apegenin, tricetin, heptamethoxyflavone (e.g-parsley, celery)

• Flavanones-compounds:-dihydroquercetin, hesperetin (e.g-orange juice)

• Flavanols-compounds-taxifolin (e.g-cocoa, chocolates)• Catechins-compounds-egcg(epigallocatechin gallate) (e.g-

tea, apricot)• Isoflavones-compounds:- genistein (e.g-soy, cheese)• Anthocyanins-componds-cyaniding (e.g-grapes, strawberry)

Strategy#2 lifestyle strategy for cancer prevention

• Maintain a healthy body weight.• Be active, whether you walk with friends or sign

up for yoga class, set a fitness goal.• Don’t miss regular check –ups with doctor• Reduce your sodium intake.• Switch to whole grains. Instead of white rice go

for brown rice.• Choose water when you are thirsty. Reduce

intake of sweet drinks such as iced tea• Avoid smoked or grilled food

• Quit smoking

• Protect your skin

• Limit red meat and animal fat

• Know your personal and family medical history

• Get screened for cancer regularly

• Increase your physical activity

Modalities of treatment:

• 1-local therapy:

– -surgery.

– -radiation therapy.

• 2-systemic treatment:

– chemotherapy.

– Monoclonal antibodies.

– Radioactive material.

• 3-supportive care.

• 4-non-conventional therapy.

Surgery:

• Surgery was the first modality used successfully in the treatment of cancer.

• It is the only curative therapy for many common solid tumors.

• The most important determinant of a successful surgical therapy are the absence of distant metastases and no local infiltration.

Cont:

• Microscopic invasion of surrounding normal tissue will necessitate multiple frozen section.

• Resection or sampling of regional lymph node is usually indicated.

• Surgery may be used for palliation in patients for whom cure is not possible.

• Has significant role in cancer prevention.

Surgery for prevention:

• Patients with conditions that predispose them to certain cancers or with genetic traits

Associated with cancer can have normal life span with prophylactic surgery.

-colectomy .

-oophorectomy.

-thyroidectomy.

-removal of premalignant skin lesion .

Radiation therapy:

Radiation therapy:

• Radiation therapy: is a local modality used in the treatment of cancer .

• Success depend in the difference in the radio sensitivity between the tumor and normal tissue.

• It involves the administration of ionizing radiation in the form of x-ray or gamma rays to the tumor site.

• Method of delivery: External beam(teletherapy).

Internal beam therapy(Brachytherapy).

BRACHYTHERAPY

• Internal radiation treatment achieved byimplanting radioactive material directly intothe tumor or very close to it.

• Sometimes called internal radiation therapy.

• Prefix “brachy” – from Greek for “short range”

WHY BRACHYTHERAPY

• Delivering the high dose of radiation to the

tumor

• Sparing of the surrounding normal tissues

• Delivered in a short period of time

– Tumor repopulation

• Limited to localized tumors

TELETHERAPY

• Teletherapy or External Beam Radiation

Therapy" involves delivery of therapeutic

radiation from a source

• that is placed away

• from the body.

Cont:

• Radiation therapy is planned and performed by a team of nurses, dosimetrists,physician and radiation oncologist.

• A course of radiation therapy is preceded by a simulation session in which low-energy beam are used to produce radiograghic images that indicate the exact beam location.

Cont:

• Radiation therapy is usually delivered in fractionated doses such as 180 to 300 cGy per day,five times a week for a total course of 5-8 weeks.

• Radiation therapy with curative intent is the main treatment in limited stage Hodgkin’s disease,someNHL,limited stage of prostate,gynecologictumors&CNS tumor .

• Also can use in palliative &emergency setting.

DOSE

• The amount of radiation used in photon radiation therapy is measured in gray (Gy),

• A unit of absorbed radiation equal to the dose of one joule of energy absorbed per kilogram of matter, or 100 rads.

• For curative cases, the typical dose for a solid epithelial tumor ranges from 60 to 80 Gy, while lymphomas are treated with 20 to 40 Gy.

• Preventive (adjuvant) doses are typically around 45–60 Gy in 1.8–2 Gy fractions (for breast, head, and neck cancers.)

Complication of radiation:

• There is two types of toxicity ,acute and long term toxicity.

• Systemic symptoms such as Fatigue,local skin reaction,GI toxicity,oropharyngeal mucositis&xerostomia.myelosuppression.

• Long-term sequelae:may occur many months or years after radiation therapy.

• Radiation therapy is known to be mutagenic,carcinogenic,and teratogen,and having increased risk of developing both secondary leukemia and solid tumor.

Chemotherapy:

Chemotherapy:

• Systemic chemotherapy is the main treatment available for disseminated malignant diseases.

• Progress in chemotherapy resulted in cure for several tumors.

• Chemotherapy usually require multiple cycles.

Classification of cytotoxic drug:

• Cytotoxic agent can be roughly categorized based on their activity in relation to the cell cycle.

phase nonspecific. phase specific

cytotoxic drug

Cont :

• What is the difference between phase specific & phase non specific?…..

• Phase non-specific:

– The drugs generally have a linear dose-response curve( the drug administration ,the the fraction of cell killed).

• Phase specific:

– Above a certain dosage level,further increase in drug doesn’t result in more cell killing.but you can play with duration of infusion.

What are the chemotherapeutic agent?…..

Chemotherapeutic agents:

• Alkylating agents: Cyclophosphamide

• Antitumor antibiotic

• Antimetabolites

Antitumor Antibiotics

Cell cycle non-specific agentsVariety of mechanisms: prevents DNA replication,

RNA production,or both

Anthracyclines AnthracenedionesActinomycin D (dactinomycin) – DNA intercalator, inhibits topoisomerase II alsoBleomycin – inhibits DNA synthesis, G2-phase specificMitomycin C – functions as alkylator

They interfere with DNA and RNA growth bysubstituting for the normal building blocks of RNA and DNA.

These agents damage cells during the S phase

Commonly used to treat...... •leukemias, •cancers of the breast•ovary, •intestinal tract,

as well as other types of cancer.

Antimetabolites

Cell-cycle Directed Anti-neoplastic Drugs

Cell Cycle Phase Drug Target

Go – G1 Taxol Microtubules (stabilize)

S-Phase Ara-C (Cytosine arabinoside)

DNA synthesis

S- G2 VP-16 (Etoposide) Topoisomerase II

M Vinca-alkaloidsTaxol

Microtubule disruptersMicrotubule stabilizer

Non-cell-cycle specific Alkylating agents:Cis-platinumCyclophosphamide

Nucleophiles (e.g. DNA)

Complication of Chemotherapy:

• Every chemotherapeutic will have some deleterious side effect on normal tissue .

• E.G; Myelosuppression,nausea&vomiting,

Stomatitis,and alopecia are the most frequently observed side effects.

• Chemotherapy targets cells which are dividing rapidly.

• Chemotherapy cannot distinguish between normal cells and cancer cells

• Healthy Cells which have a high rate of growth and multiplication include cells of the bone marrow, hair, GI mucosa and skin.

Combined Modality Therapies for Cancer

Surgery and Radiation

Adjuvant Chemotherapy: Surgery and Chemotherapy

Radio-sensitizers: Chemotherapy and Radiation

Chemotherapy and Host-Response Modification

• Induction of Differentiation by Chemotherapeutic Agents

• Induction of Apoptosis by Chemotherapeutic Agents

Immunotherapy and Gene Therapy

Genetically Engineered T-Cells

Chemotherapy with Ultra-sonic Disruption?

Combined

Immunotherapy of Cancer

• Potentially Highly Tumor-Specific

• Can be Effective Against Disseminated Disease Including Unrecognized Micro-metastases

• Probably of Limited Value Against Extensive Advanced Disease

• Can Involve Severe, Sudden Onset Life-threatening

Treatment-limiting Side-Reactions

• Limited by Tumor Heterogeneity, Selection for Unresponsive Variants, and Emergence of Immune-Escape

Host-Response Modification in Cancer

Management

Potentially Less Intrusive than Other More-Aggressive

Modalities

Treating Host Supporting Cells to Reduce their ability to

promote tumor growth (e.g. anti-angiogenesis)

Host stromal cell interactions supporting tumor growth:

Gene Therapy for Cancer

• Potentially Highly Tumor-Specific

• Accessibility of Cell Targets Is a Major Obstacle for General Application

• May Have Great Value in Combined Modality Approaches

• Potentially Dangerous Side-Reactions from Viral Vector Delivery Agents