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Cancer: Are we closer to a cure?. Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA. Cancer is a huge public health problem. Overall mortality rates have not changed for cancer…. * Age-adjusted to 2000 US standard population.

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slide1

Cancer:

Are we closer to a cure?

Jesse Boehm, Ph.D.

Broad Institute of Harvard and MIT

Cambridge, MA

overall mortality rates have not changed for cancer
Overall mortality rates have not changed for cancer…

* Age-adjusted to 2000 US standard population.

Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised.

2001 Mortality Data–NVSR-Death Final Data 2001–Volume 52, No. 3. http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_03.pdf

but we have made huge advances in some cancers
But we have made HUGE advances in some cancers!!!!

Before Iressa treatment

After 3 months of Iressa treatment

Image provided

by B. Johnson

the fundamentals of cancer
The Fundamentals of Cancer
  • What is cancer?
  • Molecular causes of cancer
  • How faulty genes are involved
  • How a cancer cell becomes dangerous
what is cancer
What is Cancer?
  • An uncontrolled growth of cells
  • A genetic disease
  • A family of similar diseases

newscenter.cancer.gov

an uncontrolled growth of cells

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An Uncontrolled Growth of Cells

normal

skin

skin cancer

non-dividing

cells

dividing cells

structural

support

  • Healthy cells turn into the enemy
    • divide too quickly or abnormally
    • become abnormal shapes and sizes
    • grow in all directions
  • Cells stop listening to the body, which is telling them to stop!
a genetic disease

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A Genetic Disease

Normal Cells

Cancer Cells

  • Mutations in DNA can make normal cells become cancerous
  • These can be inherited or spontaneous
a family of similar diseases
A Family of Similar Diseases
  • Carcinomas: from cells which
    • protect the body from air
    • and internal fluids
  • Sarcomas: from cells in
    • supportive tissue
  • Leukemias and Lymphomas:
    • from cells in the blood and
    • immune system

newscenter.cancer.gov

the fundamentals of cancer1
The Fundamentals of Cancer
  • What is cancer?
  • Molecular causes of cancer
  • How faulty genes are involved
  • How a cancer cell becomes dangerous
common causes of cancer
Common causes of cancer
  • Chemicals (e.g. tobacco, asbestos)
  • Viruses (e.g. HPV)
  • Radiation from the sun
  • What do all of these have in common?
  • They all lead to MUTATIONS
  • in the DNA of your cells
  • They are called MUTAGENS
  • Can also be predisposed to getting cancer by inheriting mutations from parents

newscenter.cancer.gov

smoking and alcohol
Smoking and Alcohol
  • Cigarette smoking causes 87 percent of lung cancer deaths and is responsible for most cancers of the larynx, oralcavity and pharynx, esophagus, and bladder
  • Tobacco smoke contains thousands of chemical agents, including over 60 substances that are known to cause cancer.
  • Alcohol use has been implicated in the development of a number of cancers
    • Risk increases >1 drink for women or 2 drinks for men/day
causes of cancer
Causes of Cancer

What are mutations and how do

they cause normal cells to become

cancer cells?

Cancer Cells

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A

A

A

A

A

T

T

T

T

T

G

G

G

G

C

C

C

C

What Happens Normally?

Normal DNA

DNA Bases

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A

A

A

A

A

A

A

A

T

T

T

T

T

G

G

G

G

G

G

C

C

C

C

C

C

What Happens Normally?

Normal DNA

mRNA

DNA is transcribed

(copied) to RNA

A

A

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A

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A

A

A

A

A

A

T

T

T

T

T

G

G

G

G

G

G

C

C

C

C

C

C

What Happens Normally?

Normal DNA

mRNA

Normal Protein

amino

acids

Translation:

Proteins are made

from mRNA

A

A

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A

A

A

A

T

T

T

T

G

G

G

G

C

C

C

C

A Mutation Occurs

Changed DNA

DELETION

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A

A

A

A

A

T

T

T

T

T

G

G

G

G

G

G

C

C

C

C

C

C

A Mutant Protein is Made

Changed DNA

Changed mRNA

Normal Protein

A

A

DELETION

A

A

Abnormal/ Mutant Protein

A

A

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A

A

A

A

A

T

T

T

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G

G

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C

C

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C

A Mutant Protein is Made

Changed DNA

Normal Protein

Abnormal/ Mutant Protein

the cell cycle controls cell division
The Cell Cycle Controls Cell Division

Cells divide (mitosis)

Growth

Cell Cycle

Growth

DNA Synthesis

the cell makes sure that there are no problems
The Cell Makes Sure That There are no Problems

Did division go correctly?

Cell Cycle

Am I ready to divide?

Am I big enough?

Is my DNA copied correctly?

the cell cycle has checkpoints
The Cell Cycle Has Checkpoints

Did division go correctly?

Cell Cycle

Am I ready to divide?

Am I big enough?

Is my DNA copied correctly?

the normal protein functions at a cell cycle checkpoint
The Normal Protein Functions at a Cell Cycle Checkpoint

Cell Cycle

Normal Protein

Is my DNA copied correctly?

the mutant protein allows the cell to divide out of control
The Mutant Protein Allows The Cell to Divide Out of Control

Cell Cycle

Normal Protein

go!

Abnormal/ Mutant Protein

I can’t stop and check if the DNA has been copied correctly!!!

the fundamentals of cancer2
The Fundamentals of Cancer
  • What is cancer?
  • Molecular causes of cancer
  • How faulty genes are involved
  • How a cancer cell becomes dangerous
how faulty genes are involved
How Faulty Genes are Involved
  • Not every gene leads to cancer when mutated
  • Mutations in two specific categories of genes can lead to cancer
    • Tumor-Suppressor Genes
    • Oncogenes
how faulty genes are involved1
How Faulty Genes are Involved
  • Not every gene leads to cancer when mutated
  • Mutations in two specific categories of genes can lead to cancer
    • Tumor-Suppressor Genes
    • Oncogenes
inactivated tumor suppressor genes lead to cancer
Inactivated Tumor Suppressor Genes Lead to Cancer
  • Tumor Suppressor (TS) genes normally inhibit cell growth
  • Mutations in TS genes may inactivate them,
  • so that they cannot stop cell-growth
  • TS genes include p53 and BRCA1/2

cell

TS gene

how faulty genes are involved2
How Faulty Genes are Involved
  • Not every gene leads to cancer when mutated
  • Mutations in two specific categories of genes can lead to cancer
    • Tumor-Suppressor Genes
    • Oncogenes
activated oncogenes lead to cancer
Activated Oncogenes Lead to Cancer
  • Oncogenes normally promote cell growth carefully
  • Mutations in oncogenes may over-activate them,
  • so that they always promote cell-growth
  • One well-known oncogene is called RAS

cell

oncogene

mutations in specific genes turn a normal cell into a cancer cell

RAS

RAS

p53

p53

Mutations in Specific Genes Turn a Normal Cell into a Cancer Cell

Mutate tumor suppressor genes, turning these genes OFF

Mutate oncogenes, turning these genes ON

1 2 3 4 5 6…..

mutations

normal cell cancer cell

the fundamentals of cancer3
The Fundamentals of Cancer
  • What is cancer?
  • Molecular causes of cancer
  • How faulty genes are involved
  • How a cancer cell becomes dangerous
slide37

Benign vs. Malignant

Benign: A non-malignant tumor lacking the ability

to invade surrounding normal tissue

Malignant: A tumor that tends to grow, has the capacity to

invade nearby tissue and spreads through the

blood stream

adapted from “Concise Dictionary of Biomedicine and Molecular Biology,” Pei-Show Juo, 1996

how cancer cells become dangerous
How cancer cells become dangerous
  • A cancer cell on its own will not cause you harm
  • To become the disease “Cancer” the cell must:
    • 1) Form a tumor (at least)
    • 2) Recruit a blood supply
      • = angiogenesis
      • (solid tumors only)
    • 3) Spread to other parts of the body
    • = metastasis
    • (advanced stages)
slide39

Metastasis

Cancer cells enter blood vessels

Cells travel through the blood stream to distant sites

Cells then invade new tissues, and begin to grow

there are different types of treatments
There are different types of treatments

Drugs (chemotherapy)

Radiation

Surgery

cancer can be local or metastatic
Cancer can be local or metastatic

local (one primary tumor)

metastatic (secondary tumors)

cancer therapy local and systemic
Cancer therapy: local and systemic

Rx

LOCAL: surgery and radiation

SYSTEMIC: chemotherapy, etc.

why need targeted therapy
Why need targeted therapy?
  • The problem of Selectivity of chemotherapy and radiation

normal cells

cancer cells

why need targeted therapy1
Why need targeted therapy?
  • The problem of Selectivity of chemotherapy and radiation

normal cells

cancer cells

why need targeted therapy2
Why need targeted therapy?
  • The problem of Selectivity of chemotherapy and radiation

normal cells

cancer cells

problem with selectivity leads to side effects
Problem with selectivity leads to side effects
  •  SIDE EFFECTS!
    • hair follicles: hair loss
    • bone marrow:  immune defense,

anemia, clotting problems

    • gut lining: diarrhea
    • skin: flaky/scaly skin

normal cells

cancer cells

how can we improve cancer therapy

Normal cell

How can we improve cancer therapy?
  • Pick a better TARGET!

Cancer cell

points to remember
Points to remember
  • Cancer is a family of similar diseases, not just one!
    • Different cancers have different causes, treatments and outcomes
  • Cancer is caused by MUTATIONS
    • Prevent your exposure to mutagens!
  • A tumor causes a patient harm by becoming malignant and metastasizing
  • By learning more about cancer we are developing new,
  • “smarter” cancer drugs
    • More effective
    • Fewer side effects
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