Lung Cancer: Stages, Treatments and
Targeted Therapies
David Barbie, M.D.
Lowe Center for Thoracic Oncology
Dana-Farber Ca...
Lung Cancer Incidence and Mortality in U.S.
KRAS Mutation
~30%
~50%
~90%
Lung Cancer Stages and Treatments
Lung Cancer Stages and Treatments
Stage 1: Localized
Lung Cancer Stages and Treatments
Stage 1: Localized
Stage 2: Larger (> 5 cm) or spread to local lymph nodes

Surgery, +/-...
Lung Cancer Stages and Treatments
Stage 1: Localized
Stage 2: Larger (> 5 cm) or spread to local lymph nodes

Surgery, +/-...
Lung Cancer Stages and Treatments
Stage 1: Localized
Stage 2: Larger (> 5 cm) or spread to local lymph nodes

Brain

Surge...
Oncogenes are the Jammed Accelerators
of Cancer Cells
BCR-ABL -

BCR-ABL +

Shtivelman et al. Nature 1985;315:550
Daley et al. Science 1990;247:824
Buchdunger et al. Cancer Res...
Lynch et al. NEJM 2004;350:2129
Paez et al. Science 2004;304:1497
Mok et al. NEJM 2009;361:947
Better than chemotherapy,
but tumors become resistant
after 10-12 months

Mok et al. NEJM 2009;361:947
Genomic complexity of lung cancer

CML

Lung Adenocarcinoma

http://www.path.cam.ac.uk
http://www.utoronto.ca/cancyto
Lung Cancer Then and Now
Many different oncogenes can get jammed

No known
genotype

1984 - 2003

No known
genotype

2004
...
Chemotherapy Targets the
Engine, Targeted Therapy the Accelerator

EGFR inhibitor
ALK inhibitor
BRAF inhibitor
Carboplatin...
DFCI Patient with NSCLC and BRAF
mutation treated with Dabrafenib

August 10, 2012

September 19, 2012

Courtesy of Stepha...
MSKCC Patient with NSCLC and BRAF
mutation treated with Dabrafenib

February 2012

June 2012

Courtesy of Gregory Riely, M...
KRAS is Difficult To Target Directly

KRAS inhibitor – failed clinical trials
Alternatives to Targeting KRAS

1. Block known downstream pathways (between pedal and engine)

Also failing in clinical tr...
Alternatives to Targeting KRAS

1. Block known downstream pathways (between pedal and engine)

XX

Also failing in clinica...
Alternatives to Targeting KRAS

2. Use genomics to identify currently unknown pathways
needed for survival (that keep car ...
CYT387 Impairs Viability of Lung cancer Cells
A549 Lung Cancer Cells
DMSO

CYT387 (5mM)
Activity of CYT387 in Kras-driven Murine Lung Cancer
Murine KRAS-Driven Lung Cancer
CYT387 100mg/kg/d

H

Baseline

H

Wee...
Activity of CYT387 in Kras-driven Murine Lung Cancer
H
E

pA
ST
T3

A

B

Uee
n ad
t t
r

2m
5
µ

C

2m
5
µ

D

Tor an
a t...
Alternatives to Targeting KRAS

Blocking multiple unique pathways
Alternatives to Targeting KRAS

Blocking multiple unique pathways

X
X

X

X
Activity of CYT387 in Kras-driven Murine Lung Cancer
KrasLSL-G12D/WT;p53flox/flox model with established tumor burden

*p<...
Activity of CYT387 in Kras-driven Murine Lung Cancer
KrasLSL-G12D/WT;p53flox/flox model with established tumor burden

*p<...
Immunotherapy – “Immune Checkpoint Blockade”
Immunotherapy – “Immune Checkpoint Blockade”
Immunotherapy – “Immune Checkpoint Blockade”

PD-L1
PD-L1

PD-L1
Immunotherapy – “Immune Checkpoint Blockade”
T cell
T cell
PD1
PD1
PD-L1

PD-L1

PD-L1
PD1

T cell
Immunotherapy – “Immune Checkpoint Blockade”
T cell

X

T cell

PD1

X

PD1
PD-L1

PD-L1

PD-L1

T cell

X

PD1
Immunotherapy – “Immune Checkpoint Blockade”
T cell

PD-L1 targeted
drugs

T cell

X

PD1

X

PD1
PD-L1

PD-L1

PD-L1

T c...
Immunotherapy – “Immune Checkpoint Blockade”
T cell
T cell
PD1
PD1

PD1

T cell
Immunotherapy – “Immune Checkpoint Blockade”

T cell
T cell
PD1
PD1

PD1

T cell
Summary

• Lung cancer can be treated with a
combination of surgery, radiation, and
chemotherapy depending on the stage
Summary

• Lung cancer can be treated with a
combination of surgery, radiation, and
chemotherapy depending on the stage
• ...
Summary

• Lung cancer can be treated with a
combination of surgery, radiation, and
chemotherapy depending on the stage
• ...
Lung Cancer Stages, Treatments and Targeted Therapies
Lung Cancer Stages, Treatments and Targeted Therapies
Upcoming SlideShare
Loading in...5
×

Lung Cancer Stages, Treatments and Targeted Therapies

3,835

Published on

Audio and slides for this presentation are available on YouTube: http://youtu.be/rt_O7m2eTYA

David Barbie, MD, of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, discusses the stages of lung cancer, how the disease is treated, and new targeted therapies for patients. This presentation was originally given at Dana-Farber's "Living with Lung Cancer" forum on Nov. 2, 2013.

Published in: Health & Medicine
1 Comment
17 Likes
Statistics
Notes
  • Thanks! For better options in treatment, please, visit cancercuremedicine.com, read: http://www.amazon.com/s/ref=nb_sb_noss_1/183-5035389-4416932?url=search-alias%3Daps&amp;field-keywords=travis+christofferson
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total Views
3,835
On Slideshare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
1
Comments
1
Likes
17
Embeds 0
No embeds

No notes for slide

Transcript of "Lung Cancer Stages, Treatments and Targeted Therapies"

  1. 1. Lung Cancer: Stages, Treatments and Targeted Therapies David Barbie, M.D. Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute Assistant Professor of Medicine, Harvard Medical School November 2, 2013
  2. 2. Lung Cancer Incidence and Mortality in U.S. KRAS Mutation ~30% ~50% ~90%
  3. 3. Lung Cancer Stages and Treatments
  4. 4. Lung Cancer Stages and Treatments Stage 1: Localized
  5. 5. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy
  6. 6. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery
  7. 7. Lung Cancer Stages and Treatments Stage 1: Localized Stage 2: Larger (> 5 cm) or spread to local lymph nodes Brain Surgery, +/-chemotherapy Stage 3: Locally advanced Chemotherapy and radiation, +/- surgery Bone Stage 4: Advanced/metastatic Chemotherapy +/- palliative radiation Liver Adrenals
  8. 8. Oncogenes are the Jammed Accelerators of Cancer Cells
  9. 9. BCR-ABL - BCR-ABL + Shtivelman et al. Nature 1985;315:550 Daley et al. Science 1990;247:824 Buchdunger et al. Cancer Res 1996;56:100 Deininger et al. Blood 1997;90:3691 Druker, BJ. Nat Med 2009;15:1149
  10. 10. Lynch et al. NEJM 2004;350:2129 Paez et al. Science 2004;304:1497
  11. 11. Mok et al. NEJM 2009;361:947
  12. 12. Better than chemotherapy, but tumors become resistant after 10-12 months Mok et al. NEJM 2009;361:947
  13. 13. Genomic complexity of lung cancer CML Lung Adenocarcinoma http://www.path.cam.ac.uk http://www.utoronto.ca/cancyto
  14. 14. Lung Cancer Then and Now Many different oncogenes can get jammed No known genotype 1984 - 2003 No known genotype 2004 Erlotinib X X 2009 Crizotinib 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
  15. 15. Chemotherapy Targets the Engine, Targeted Therapy the Accelerator EGFR inhibitor ALK inhibitor BRAF inhibitor Carboplatin + Alimta or Taxol
  16. 16. DFCI Patient with NSCLC and BRAF mutation treated with Dabrafenib August 10, 2012 September 19, 2012 Courtesy of Stephanie Cardarella, MD, DFCI Thoracic Oncology
  17. 17. MSKCC Patient with NSCLC and BRAF mutation treated with Dabrafenib February 2012 June 2012 Courtesy of Gregory Riely, MD, Memorial Sloan-Kettering Cancer Center
  18. 18. KRAS is Difficult To Target Directly KRAS inhibitor – failed clinical trials
  19. 19. Alternatives to Targeting KRAS 1. Block known downstream pathways (between pedal and engine) Also failing in clinical trials
  20. 20. Alternatives to Targeting KRAS 1. Block known downstream pathways (between pedal and engine) XX Also failing in clinical trials X X
  21. 21. Alternatives to Targeting KRAS 2. Use genomics to identify currently unknown pathways needed for survival (that keep car from crashing) TBK1
  22. 22. CYT387 Impairs Viability of Lung cancer Cells A549 Lung Cancer Cells DMSO CYT387 (5mM)
  23. 23. Activity of CYT387 in Kras-driven Murine Lung Cancer Murine KRAS-Driven Lung Cancer CYT387 100mg/kg/d H Baseline H Week 16 Kwok Wong Travis Cohoon
  24. 24. Activity of CYT387 in Kras-driven Murine Lung Cancer H E pA ST T3 A B Uee n ad t t r 2m 5 µ C 2m 5 µ D Tor an a t el e xe o 2m 5 µ E 2m 5 µ F C an Yl e To 2m 5 µ 2m 5 µ
  25. 25. Alternatives to Targeting KRAS Blocking multiple unique pathways
  26. 26. Alternatives to Targeting KRAS Blocking multiple unique pathways X X X X
  27. 27. Activity of CYT387 in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
  28. 28. Activity of CYT387 in Kras-driven Murine Lung Cancer KrasLSL-G12D/WT;p53flox/flox model with established tumor burden *p<0.01 **p<0.0001 Treatment well tolerated other than initial gavage trauma CYT387: 100 mg/kg/daily by oral gavage Selumetinib: 25 mg/kg/twice daily by oral gavage Kwok Wong Travis Cohoon
  29. 29. Immunotherapy – “Immune Checkpoint Blockade”
  30. 30. Immunotherapy – “Immune Checkpoint Blockade”
  31. 31. Immunotherapy – “Immune Checkpoint Blockade” PD-L1 PD-L1 PD-L1
  32. 32. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD-L1 PD-L1 PD-L1 PD1 T cell
  33. 33. Immunotherapy – “Immune Checkpoint Blockade” T cell X T cell PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
  34. 34. Immunotherapy – “Immune Checkpoint Blockade” T cell PD-L1 targeted drugs T cell X PD1 X PD1 PD-L1 PD-L1 PD-L1 T cell X PD1
  35. 35. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
  36. 36. Immunotherapy – “Immune Checkpoint Blockade” T cell T cell PD1 PD1 PD1 T cell
  37. 37. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage
  38. 38. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success
  39. 39. Summary • Lung cancer can be treated with a combination of surgery, radiation, and chemotherapy depending on the stage • We continue to develop new ways to target lung cancer more directly, with increasing success • With combinations of these new targeted therapies the future is very bright

×