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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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Cancer are we closer to a cure

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

Cancer is a huge public health problem


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


Cancer are we closer to a cure

…and we are on the verge of many more successes!!!!


Cancer are we closer to a cure

We have made HUGE advances in prevention!!!!


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


How could a mutant protein make cells divide out of control

How Could a Mutant Protein Make Cells Divide Out of Control?

?

mutant protein cancer cells

mutant DNA


Cancer are we closer to a cure

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


Cancer are we closer to a cure

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


Cancer are we closer to a cure

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

Normal Protein

amino

acids

Translation:

Proteins are made

from mRNA

A

A


Cancer are we closer to a cure

A

A

A

A

T

T

T

T

G

G

G

G

C

C

C

C

A Mutation Occurs

Changed DNA

DELETION


Cancer are we closer to a cure

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


Cancer are we closer to a cure

A

A

A

A

A

T

T

T

T

T

G

G

G

G

C

C

C

C

A Mutant Protein is Made

Changed DNA

Normal Protein

Abnormal/ Mutant Protein


How could a mutant protein make cells divide out of control1

How Could a Mutant Protein Make Cells Divide Out of Control?

?

mutant protein cancer cells


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 cellcancer 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


Cancer are we closer to a cure

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)


Cancer are we closer to a cure

Metastasis

Cancer cells enter blood vessels

Cells travel through the blood stream to distant sites

Cells then invade new tissues, and begin to grow


Cancer treatment

Tumor

Cancer treatment

Heart

Lung


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


Killing a fly with a cannon ball

Killing a fly with a cannon ball?


Cancer are we closer to a cure

We can kill the fly but…


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


Cancer are we closer to a cure

Thank you!


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