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- Systems Biology in Molecular and Cellular Biology
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1. Integrated view on a eukaryotic osmoregulation system
- Prof. Stefan Hohmann
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2. Systems biology of the cell cycle
- Prof. Bela Novak
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3. Interactome networks and human disease
- Prof. Marc Vidal
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4. Control feedback and cellular responses
- Prof. Francis J. Doyle III
- Systems Biology in Metabolism
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5. Impact of systems biology on metabolic engineering
- Prof. Jens Nielsen
- Computational Concepts in Systems Biology
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6. Systems biology graphical notation (SBGN)
- Prof. Huaiyu Mi
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7. Garuda platform: re-imagining connectivity in medicine
- Dr. Samik Ghosh
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8. A versatile platform for multilevel modeling of physiological systems
- Dr. Yoshiyuki Asai
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9. A systems biology approach to oncology drug development
- Dr. Birgit Schoeberl
- Systems Biology in Development and Diseases
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11. A systems approach to implementation of personalized cancer therapy
- Prof. Gordon B. Mills
- Applications of Systems Biology in Drug Discovery and Biotechnology
Printable Handouts
Navigable Slide Index
- Introduction
- Targeting specific genetic changes
- Targeted therapy for cancer (1)
- Targeted therapy for cancer (2)
- Targeted therapy for cancer (3)
- Systems biology
- Adaptive resistance: PI3K pathway
- Unexpected high failure of targeted therapeutics
- Treat the tumor that threatens the patient
- Intratumoral heterogeneity in renal cancer
- Genomic events converge into several pathways
- Convergent tumoral heterogeneity evolution (1)
- Convergent tumoral heterogeneity evolution (2)
- Concordance of genomic alterations in tumors
- Acquisition of constitutively active ESR1 mutation
- Role of ‘liquid’ biopsy approaches & cfDNA
- Challenges & need for functional genomics
- Scope of the problem
- Aberration-based functional genomics (1)
- PIK3R1/p85a
- Aberration-based functional genomics (2)
- Identification of PIK3R1 driver mutations
- Classes of PIK3R1 mutations
- PIK3R1 R348* acts as a neomorph
- Extracellular matrix protection from therapeutics
- Genomic changes integrate at protein function
- Human proteomics atlas: RPPA
- Sparse unbiased evaluation of network space
- PARP inhibitors induce lethality in HRD cancer
- Rank-sum analysis of AZD2281 & BMN673 (1)
- Rank-sum analysis of AZD2281 & BMN673 (2)
- BKM & Olaparib demonstrate marked responses
- Duration of treatment benefit
- Rank-sum analysis of AZD2281 & BMN673 (3)
- Checkpoints as potential targets in DNA damage
- PARP & Wee1 inhibitors are effective
- Rank-sum analysis of AZD2281 & BMN673 (4)
- KRAS mutation, resistance & sensitivity marker (1)
- KRAS mutation, resistance & sensitivity marker (2)
- Synergy of PARPi & MEKi/ERKi
- PARP + MEK inhibitors are synergistic in vivo
- Mechanisms underlying in vivo synergy
- Operating model
- Rational strategy for combination therapies
- Acknowledgments note
Topics Covered
- Targeted therapy for cancer
- Adaptive resistance: PI3K pathway
- Tumor heterogeneity
- Challenges & need for functional genomics
- Identification of PIK3R1 driver mutations
- Human proteomics atlas: reverse phase protein array (RPPA)
- Checkpoint inhibition as potential targets
- Synergy, operating model & strategy for combination therapies
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Mills, G.B. (2017, April 30). A systems approach to implementation of personalized cancer therapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 1, 2024, from https://doi.org/10.69645/IQLL4058.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Gordon B. Mills has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
This is Gordon Mills
from the MD Anderson Cancer Center
where I'm the chair of the Department
of Systems Biology,
the co-director of the Khalifa Institute
for Personalized Cancer Therapy,
the director of the Kleberg Center
for Molecular Markers,
and co-director
of Women's Cancer Moonshot.
I'm going to present today a systems approach
to the implementation
of personalized cancer therapy.
Some of what I will be presenting
would also be characterized
as a systematic approach
to delivering an improved response
for our patients in terms of
targeted therapy and immunotherapy.
0:38
Today we have an opportunity
to characterize patient tumors
in the breadth and depth
that we had not been able to do
even 10 or 15 years ago.
This is allowing us to move
away from relatively blunt
but effective instruments
of radiation therapy and chemotherapy
to targeting the genetic aberrations
that are specific to each patient's cancer
using small molecule inhibitors,
targeting the genetic
aberrations present in the tumors,
and immune oncology agents capitalizing
on the genomic instability and new antigens
that are presented by the tumor.
This gives us an opportunity
to move away from approaches
that generally targeted
cellular proliferation
and had a limited therapeutic index
to capitalizing on the vulnerabilities
that occur when a tumor develops.
This development of tumors
results in changes
as in important signaling pathways
that leads to a much more
limited heterogeneity of the tumor
and a much more limited ability to deal
with the stress of therapy that we use.
I'll come back
to that a little bit later.