An introduction to cancer

An introduction to Cancer

SALMAN UL ISLAM2014-11-052013298039

Kyungpook National University

What is Cancer?

Cancer is a group of diseases characterized by unregulated cell growth and the invasion and spread of cells from the site of origin, or primary site, to other sites in the body.

Benign vs Malignant tumors

Slow growing Capsulated Non-invasive Do not metastasize Well differentiated Suffix “oma” e.g. Fibroma

Fast growing Non-capsulated Invasive & infiltrate Metastasize Poorly differentiated Suffix “Carcinoma” or

“Sarcoma”

Benign tumors Malignant tumors

http://medicinembbs.blogspot.kr/2011/02/neoplasia.html

Classification of cancer

There are more than 100 types of cancer. These are classified on the basis of tissue of origin.

Carcinomas: Cancers of epithelial cells. They constitute approximately 85% of all cancers.

Sarcomas: Cancers of mesoderm cells (e.g. bone, muscle).

Adenocarcinomas: Cancers of glandular tissue (e.g. breast).

Classification of cancer

“Hanahan & Weinberg defined” Hallmarks of cancer

Cancer usually causes somatic mutations

Somatic cells: All the body cells except the reproductive (germ) cells.

Germ cells: Either the egg or the sperm cell; a reproductive cell.

Almost all of the mutations identified in tumor cells are somatic mutations. These mutations are not passed on to the next generation.

Only germline mutations will be passed on to off-spring.

Cancer usually causes somatic mutations

Normal body processes regulate body net cells number

Cell proliferation, differentiation and apoptosis regulate overall net cell number in an individual.

Total 9 cells

4 cells divided4 cells died1 cell differentiatedTotal remaining cells= 9

Apoptosis is blocked in 1 cell5 cells divided3 cells died1 cell differentiatedTotal remaining cells= 11

Oncogenes and tumor suppressor genes regulate cancer

Oncogene: It is the gene mutated such that its protein product is produced in higher quantities, or has increased activity and therefore initiate tumor formation. It sometimes produces a growth factor receptor that is always in the “ON” state.

Oncogenes and tumor suppressor genes regulate cancer

Tumor suppressor gene: This gene codes for proteins that play a role in inhibiting both growth and tumor formation.

Oncogenes and tumor suppressor genes regulate cancer

Knudson’s two-hit hypothes

is

Influential factors in human carcinogenesis

Factors that play an important role in carcinogenesis include:

Environment Reproductive life Diet Alcohol Smoking

Influential factors in human carcinogenesis

Environment: Environmental agents were first correlated with specific cancers in 1775 by a British surgeon.

Incidence of nasal and scrotal cancer is high in chimney sweeps.

Unprotected exposure to sun leads to skin cancer.

Influential factors in human carcinogenesis

Reproductive life: Cancer has a great relation with reproductive life.

Women having children have a reduced risk of breast cancer. The risk is higher in Nuns.

Nuns have a low incidence of cervical cancer, which is caused by sexually transmitted human papillomaviruses.

Kaposi’s sarcoma, which requires immunosuppressive conditions (AIDS) is predominant in Kenyan males.

Influential factors in human carcinogenesis

Diet: It is one of the most influential factors of cancer. Stomach cancer is a predominant cancer in the

Japanese population and a minor cancer in the population of the USA.

Influential factors in human carcinogenesis

Alcohol: Chronic alcohol drinking increases the risk of cancer of the mouth, esophagus, and breast, and probable evidence for increased risk of liver cancer.

Daily alcohol intake should not exceed 28g (approx. ¼ of a bottle of wine).

Genetics and alcoholism. Nature Reviews

Influential factors in human carcinogenesis

Smoking: Smoking causes lungs cancer; the main cancer worldwide. It is also implicated in pancreatic, bladder, kidney, mouth, stomach, and liver cancer.

Age-adjusted cancer death rates, USA,1930-2010

Principles of Cancer therapies

Surgery was the earliest strategy used against cancer. It is not precise as cancer cells spread from the primary site.

Chemotherapy is preferred, either for cytostatic or cytotoxic effect.

The ultimate goal of chemotherapy is to damage the DNA for inducing apoptosis in cancer cells.

Chemotherapeutic agents having higher value of therapeutic index are considered safe.

Therapeutic index

Therapeutic index refers to the relationship between toxic and therapeutic dose. 

Where: TD50 is the dose of drug that causes a toxic response in 50% of the population and ED50 is the dose of drug that is therapeutically effective in 50% of the population.

Clinical Trials for new anti-cancer drugs

Clinical trials are required for testing the new drugs in humans.

CERN Foundation, Collaborative Ependymoma Research Network, ohio

Single-blind and double-blind study

Single blind study: Patients don’t know whether they are taking treatment or placebo (control dosage forms).

Double blind studies: Both, patient and doctor, are in dark.

Important molecular targets for anti-cancer drugs

There are several families of “star players” in the story of carcinogenesis to be targeted.

These interconnect many pathways and can exert several effects in response to a specific signal.

Protein kinases and Ras protein

p53 and Retinoblastoma gene (Rb)

Cancer genome

The sequencing and mapping of human genome has paved the way of cancer genomics.

Learning the difference between genome of cancer and a normal cell will have a great contribution in designing more powerful and specific drugs.

International Cancer Genome Consortium (ICGC) is trying to characterize at least 50 classes of cancer, creating an open access to the entire research community.

The international SNP Map Working Group is anlazing single nucleotide polymorphism (SNPs).

It will help in identifying mutations within the genome that may be linked with cancer.

Summary

Cancer is the uncontrolled and unregulated growth of cells which metastasize throughout the body.

Cancer is a genome disease at the cellular level.

Changes in lifestyle can affect cancer risk. Protein kinases are important molecules in

carcinogenesis. Cancer genomics is being used to define

molecular targets for tumor-specific effects.