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RAS oncogene

RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

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Page 1: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

RAS oncogene

Page 2: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Research goals

Page 3: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Outline

Page 4: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

RAS oncogene

Page 5: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Molecular characterization

Page 6: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Mammalian counterpart

Page 7: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Point mutations

Page 8: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Transforming oncogene

Page 9: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Biochemical properties

Page 10: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras family

Page 11: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras GDP-GTP Cycle

Page 12: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras membrane localization

Page 13: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras signaling network

Page 14: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras mutations

Page 15: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Mutation spectrum

Page 16: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

GTP hydrolysis

Page 17: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Oncogenic driver

Page 18: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Neoplastic transformation

Page 19: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras signaling

Page 20: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras membrane association

Page 21: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras inhibition

Page 22: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Direct inhibition

Page 23: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Kinase inhibitors

Page 24: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

MAPK pathway

Page 25: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

MAPK pathway

Page 26: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Feedback activation

Page 27: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

MEKi combinations

Page 28: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Therapeutic window

Page 29: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Synthetic lethality

Page 30: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Oncogene addiction

Page 31: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Synthetic lethal interactions

Page 32: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Dissecting the contribution

Page 33: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

siRNA platform

Page 34: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

KRAS addiction

Page 35: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Ras effector and stress response

Page 36: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Single node dependency

Page 37: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Private node dependency

Page 38: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Paired node dependency

Page 39: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Paired node pair dependencies

Page 40: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Private node pair dependency

Page 41: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Gene paralog combinations

Page 42: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Deconvolution

Page 43: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Knockdown

Page 44: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Cell cycle arrest

Page 45: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Autophagy pathways

Page 46: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

RAF kinase and autophagy

Page 47: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Co-targeting

Page 48: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

MAPK and autophagy

Page 49: RAS oncogene · 2020. 12. 18. · Ras signaling & oncogenesis 3. Targeting Ras and its signaling network 4. Synthetic lethal partners of the KRAS oncogene S. Identify optimal target

Acknowledgment