swathi ramakrishnan oncology for scientists …swathi ramakrishnan oncology for scientists 9.8.15...

SWATHI RAMAKRISHNAN ONCOLOGY FOR SCIENTISTS

9.8.15 SWATHI.RAMAKRISHNAN@ROSWELLPARK.ORG

Hallmarks of cancer

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

Ways tumor cells tilt the balance to their advantage

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Proliferation signals Inhibitory signals

Apoptosis

Immortality

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)

Evading growth suppressors

7Mays Hoopes, L. L. (2010) Aging and Cell Division. Nature Education 3(9):55

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)

Genomic instability

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DNA damage repair pathways

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Chromosome instability

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Normal Cancer

Cellular energetics

SA Biosciences

Michael Ohh; Tumor strengths and frailties: Cancer SUMmOns Otto's metabolism Nature Medicine 18, 30–31 (2012) 14

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?

Inducing angiogenesis

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Region of insufficent blood supply

Angiogenic Factors

Antiangiogenic Factors

1 mm3

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)

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?

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

Tumor heterogeneity

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Emerging hallmark-Epigenetics

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Targeting therapy towards cancer

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● Questions?