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Drugging the cancer genome to overcome drug resistance
Annals of Oncology 26 (Supplement 2): ii1, 2015 doi:10.1093/annonc/mdv079.2
Plenary session 1: Opening Ceremony O1:2
DRUGGING THE CANCER GENOME TO OVERCOME DRUG RESISTANCE
P. Workman The Institute of Cancer Research, London, United Kingdom
In addition to exploring these concepts I will present recent work from my laboratory that demonstrates the potential of PI3 kinase and HSP90 inhibitors to contribute to overcoming and preventing cancer evolution and drug resistance.
abstracts
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 17, 2016
We are facing a major transformational inflection point in the history of cancer drug discovery. We have successfully transitioned from the first golden age of cytotoxic chemotherapy into the second golden age of molecularly targeted drugs that exploit the molecular addictions and vulnerabilities of cancer cells. But despite the successes, we have encountered the same therapeutic roadblock: the inexorable and enduring problem of drug resistance. On the more optimistic side, we now understand the fundamental processes that underpin drug resistance. These involve genetic instability;
genetic and phenotypic heterogeneity; and evolution under the selective pressure of the tumour microenvironment and therapeutic challenge. This understanding arms us with knowledge upon which to mount an attack on cancer evolution that will lead us into the third golden age of cancer drug discovery with the expectation of achieving long term control and eventual cure for many patients. I propose a 3-pronged attack involving: 1. Extending the druggable genome (beyond the current 5% coverage of targeted cancer genes) to provide drugs that cover all elements of the network of oncogenic mechanisms 2. Use of our expanded armamentarium of drugs in intelligent combinations to reduce the opportunity for bypass mechanisms 3. Design of drugs that target key fundamental drivers of cancer evolution and drug resistance which may be different from targets that exploit addictions and synthetic lethalities.
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Plenary session 1: Opening Ceremony O1:2
DRUGGING THE CANCER GENOME TO OVERCOME DRUG RESISTANCE
P. Workman The Institute of Cancer Research, London, United Kingdom
In addition to exploring these concepts I will present recent work from my laboratory that demonstrates the potential of PI3 kinase and HSP90 inhibitors to contribute to overcoming and preventing cancer evolution and drug resistance.
abstracts
Downloaded from http://annonc.oxfordjournals.org/ by guest on March 17, 2016
We are facing a major transformational inflection point in the history of cancer drug discovery. We have successfully transitioned from the first golden age of cytotoxic chemotherapy into the second golden age of molecularly targeted drugs that exploit the molecular addictions and vulnerabilities of cancer cells. But despite the successes, we have encountered the same therapeutic roadblock: the inexorable and enduring problem of drug resistance. On the more optimistic side, we now understand the fundamental processes that underpin drug resistance. These involve genetic instability;
genetic and phenotypic heterogeneity; and evolution under the selective pressure of the tumour microenvironment and therapeutic challenge. This understanding arms us with knowledge upon which to mount an attack on cancer evolution that will lead us into the third golden age of cancer drug discovery with the expectation of achieving long term control and eventual cure for many patients. I propose a 3-pronged attack involving: 1. Extending the druggable genome (beyond the current 5% coverage of targeted cancer genes) to provide drugs that cover all elements of the network of oncogenic mechanisms 2. Use of our expanded armamentarium of drugs in intelligent combinations to reduce the opportunity for bypass mechanisms 3. Design of drugs that target key fundamental drivers of cancer evolution and drug resistance which may be different from targets that exploit addictions and synthetic lethalities.
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].