1. Broad Institute of Harvard and MIT
Cancer:
Are we closer to a cure?
Jesse Boehm, Ph.D.
Broad Institute of Harvard and MIT
Cambridge, MA

2. Cancer is a huge public health problem

3. 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.

4. But we have made HUGE advances in some cancers!!!!
Before Iressa treatment
After 3 months of Iressa treatment
Image provided
by B. Johnson

5. We have made HUGE advances in prevention!!!!

6. The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous

7. What is Cancer? An uncontrolled growth of cells A genetic disease
A family of similar diseases
newscenter.cancer.gov

8. 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!

9. A Genetic Disease
Normal Cells
Cancer Cells .
Mutations in DNA can make normal cells become cancerous
These can be inherited or spontaneous

10. 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

11. The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous

12. 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

13. Smoking and Alcohol
Cigarette smoking causes 87 percent of lung cancer deaths and is responsible for most cancers of the larynx, oral cavity 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

14. What are mutations and how do they cause normal cells to become
Causes of Cancer
What are mutations and how do
they cause normal cells to become
cancer cells?
Cancer Cells

15. How Could a Mutant Protein Make Cells Divide Out of Control?
mutant DNA
mutant protein cancer cells

16. What Happens Normally? Normal DNA A T C G A T A T C G G C A T G C A T
DNA Bases C G A T A T C G G C A T G C A T

17. What Happens Normally? Normal DNA mRNA A T A DNA is transcribed
(copied) to RNA C C G A A T A A T C G C G C G A T A G C G A T A

18. What Happens Normally? Normal DNA mRNA A T A Normal Protein C C G A A
amino
acids A A T C G C G C G
Translation:
Proteins are made
from mRNA A T A G C G A T A

19. A Mutation Occurs
Changed DNA A T C G A T
DELETION C G G C A T G C A T

20. A Mutant Protein is Made
Changed DNA
Changed mRNA
Normal Protein A T A C C G A A T
DELETION A C G C G C G A T A
Abnormal/ Mutant Protein G G C A A T A A T

21. A Mutant Protein is Made
Changed DNA A T
Normal Protein C G A T C G G C A T G C
Abnormal/ Mutant Protein A T A T

22. How Could a Mutant Protein Make Cells Divide Out of Control?
mutant protein cancer cells

23. The Cell Cycle Controls Cell Division
Cells divide (mitosis)
Growth
Cell Cycle
Growth
DNA Synthesis

24. 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?

25. 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?

26. The Normal Protein Functions at a Cell Cycle Checkpoint
Is my DNA copied correctly?

27. 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!!!

28. The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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
p53
RAS
…..
mutations
normal cell cancer cell

35. The Fundamentals of Cancer
What is cancer?
Molecular causes of cancer
How faulty genes are involved
How a cancer cell becomes dangerous

36. 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

37. 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)

38. Metastasis Cancer cells enter blood vessels
Cells travel through the blood stream to distant sites
Cells then invade new tissues, and begin to grow

39. Cancer treatment
Heart
Lung
Tumor

40. There are different types of treatments
Drugs (chemotherapy)
Radiation
Surgery

41. Cancer can be local or metastatic
local (one primary tumor)
metastatic (secondary tumors)

42. Cancer therapy: local and systemicRx
LOCAL: surgery and radiation
SYSTEMIC: chemotherapy, etc.

43. Why need targeted therapy?
The problem of Selectivity of chemotherapy and radiation
normal cells
cancer cells

44. Why need targeted therapy?
The problem of Selectivity of chemotherapy and radiation
normal cells
cancer cells

45. Why need targeted therapy?
The problem of Selectivity of chemotherapy and radiation
normal cells
cancer cells

46. Killing a fly with a cannon ball?

47. We can kill the fly but…

48. Problem with selectivity leads to side effects
hair follicles: hair loss
bone marrow:  immune defense,
anemia, clotting problems
gut lining: diarrhea
skin: flaky/scaly skin
normal cells
cancer cells

49. How can we improve cancer therapy?
Pick a better TARGET!
Normal cell
Cancer cell

50. 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

51. Thank you!