Charles Swanton

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..We argue that the failure to adopt these methods rapidly into clinical trial design will increase late stage drug attrition, waste trial resources, and risk patient harm within unselected cohorts...

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..Furthermore, this work supports efforts to identify common pathways of drug response for future drug discovery programmes...

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..A phase II trial of taxanes in patients with metastatic CIN negative CRC may be indicated...

..The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies...

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..COL4A3BP expression is increased in drug-resistant cell lines and in residual tumor following paclitaxel treatment of ovarian cancer, suggesting that it could be a target for chemotherapy-resistant cancers...

..These data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in ccRCC...

..These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity...

..Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents...

..Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples...

..A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel strategies to improve outcome in cancer...

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..These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome...

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..Our results suggest that stratifying tumor responses according to CIN status should be considered within the context of clinical trials to minimize the confounding effects of tumor CIN status on drug sensitivity...

..The relationship between CIN and prognosis supports assessment of CIN status in the clinical setting and suggests that stratifying tumours according to levels of CIN could facilitate clinical risk assessment...

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..This represents a rational approach to accelerate biomarker discovery, maximising the potential for therapeutic benefit and minimising the health economic cost of ineffective therapy...

..In this Review, we attempt to summarize the sometimes confusing findings, and critically assess those markers already in the public domain...

..Envisaging tumor growth as a Darwinian tree with the trunk representing ubiquitous mutations and the branches representing heterogeneous mutations may help in drug discovery and the development of predictive biomarkers of drug response...

..CDK10 is thus a potential biomarker for sensitivity in prospective clinical trials of patients treated with endocrine therapies...

..An improved understanding of histone and chromatin regulation in RCC biology and the consequences of intratumor heterogeneity might identify novel targets in RCC and present alternative therapeutic opportunities...

..The future management of MBC will increasingly focus on stratifying therapeutics based on individualized-tumour molecular aberrations...

..The most promising Her2-targeted strategy will likely prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her2 dimerization inhibitors...

..The challenge is how to integrate these data with biological samples to define relevant drug-resistant pathways in vivo...

..This study shows brain metastases are common phenomenon in HER2 positive advanced breast cancer patients receiving trastuzumab and also may implicate the brain as a sanctuary site for early relapse in this patient cohort...

..Functional genomics elucidation of drug resistance pathways using RNA interference (RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development...

..Our findings imply that the early stages of squamous carcinoma development are driven by a change in amplitude of EGFR signalling governed by the loss of contact inhibition...

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..This review will introduce the protein families that regulate the cell cycle, their aberrations in malignant progression and pharmacological strategies targeting this important process...

..Ongoing research will further define the relative merits of other sequences in terms of clinical outcome...

..These data show that ECM can mediate taxane sensitivity by modulating microtubule stability...

..Microtubule-stabilising agents typified by the epothilone class of drug have demonstrated promising activity in Phase II and III clinical trials...