swathi ramakrishnan oncology for scientists …swathi ramakrishnan oncology for scientists 9.8.15...
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Cancer is the Result of a Multistep Process
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What are the hallmarks of cancer?
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Maintaining the balance
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Proliferation Inhibiting growth/Apoptosis
Proliferation Inhibiting growth/Apoptosis
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Ways tumor cells tilt the balance to their advantage
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Proliferation signals Inhibitory signals
Apoptosis
Immortality
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Sustaining proliferative signaling
6Tweeny R. Kau, Jeffrey C. Way & Pamela A. Silver; Nuclear transport and cancer: from mechanism to intervention; Nature Reviews Cancer 4, 106-117 (February 2004)
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Evading growth suppressors
7Mays Hoopes, L. L. (2010) Aging and Cell Division. Nature Education 3(9):55
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Insensitivity to Anti-Growth Signals
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Enabling replicative immortality
10William C. Hahn & Robert A. Weinberg; Modelling the molecular circuitry of cancer; Nature Reviews Cancer 2, 331-341 (May 2002)
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Genomic instability
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DNA damage repair pathways
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Chromosome instability
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Normal Cancer
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Cellular energetics
SA Biosciences
Michael Ohh; Tumor strengths and frailties: Cancer SUMmOns Otto's metabolism Nature Medicine 18, 30–31 (2012) 14
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Ways tumor cells tilt the balance to their advantage
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Proliferation signals Inhibitory signals
Apoptosis
Immortality
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Can a tumor survive by itself?
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Inducing angiogenesis
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Region of insufficent blood supply
Angiogenic Factors
Antiangiogenic Factors
1 mm3
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Angiogenesis-multiple components
18Rakesh K. Jain, Emmanuelle di Tomaso, Dan G. Duda, Jay S. Loeffler, A. Gregory Sorensen & Tracy T. Batchelor; Angiogenesis in brain tumours; Nature Reviews Neuroscience 8, 610-622 (August 2007)
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Activating invasion and metastasis
Wai Leong Tam & Robert A Weinberg; The epigenetics of epithelial-mesenchymal plasticity in cancer; Nature Medicine 19, 1438–1449 (2013)
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What we have studied so far?
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Immune system
21Karin E. de Visser, Alexandra Eichten & Lisa M. Coussens; Paradoxical roles of the immune system during cancer development; Nature Reviews Cancer 6, 24-37 (January 2006)
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Multiple pathways in cancer
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Tumor heterogeneity
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Emerging hallmark-Epigenetics
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Targeting therapy towards cancer
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● Questions?