Development of Therapeutic Combinations Targeting Major Cancer Signaling Pathways

Patient-reported outcomes from POINTBREAK: The randomized, open-label, phase III study of pemetrexed (pem) + carboplatin (cb) + bevacizumab (bev) followed by maintenance pem + bev versus paclitaxel (pac) + cb + bev followed by maintenance bev in patients with stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC).

(2017) David R. Spigel et al.   JOURNAL OF CLINICAL ONCOLOGY

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health

(2015) William H. Chappell et al.   Oncotarget

Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

(2012) N Tunariu et al.   BRITISH JOURNAL OF CANCER

Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100

(2012) J. Richards et al.   CANCER RESEARCH

Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial

(2012) José Baselga et al.   LANCET

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors

(2012) Timothy R. Wilson et al.   NATURE

Combinatorial drug therapy for cancer in the post-genomic era

(2012) Bissan Al-Lazikani et al.   NATURE BIOTECHNOLOGY

Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

(2012) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

(2012) Marco Gerlinger et al.   NEW ENGLAND JOURNAL OF MEDICINE

Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy

(2012) Howard I. Scher et al.   NEW ENGLAND JOURNAL OF MEDICINE

Multi-Purpose Utility of Circulating Plasma DNA Testing in Patients with Advanced Cancers

(2012) Geraldine Perkins et al.   PLoS One

Genome Sequencing Identifies a Basis for Everolimus Sensitivity

(2012) G. Iyer et al.   SCIENCE

Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing

(2012) R. J. Leary et al.   Science Translational Medicine

Intratumor Heterogeneity: Seeing the Wood for the Trees

(2012) T. A. Yap et al.   Science Translational Medicine

Exploiting the Cancer Genome: Strategies for the Discovery and Clinical Development of Targeted Molecular Therapeutics

(2011) Timothy A. Yap et al.   Annual Review of Pharmacology and Toxicology

AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity

(2011) Sarat Chandarlapaty et al.   CANCER CELL

Reciprocal Feedback Regulation of PI3K and Androgen Receptor Signaling in PTEN-Deficient Prostate Cancer

(2011) Brett S. Carver et al.   CANCER CELL

Targeted agents: How to select the winners in preclinical and early clinical studies?

(2011) Rachel Goodwin et al.   EUROPEAN JOURNAL OF CANCER

Targeting the insulin-like growth factor signaling pathway: figitumumab and other novel anticancer strategies

(2011) Timothy A Yap et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett's Epithelium

(2011) Toshiro Sato et al.   GASTROENTEROLOGY

Effective Use of Thalidomide in the Treatment of Recurrent Metastatic Chordoma

(2011) Wen Yee Chay et al.   JOURNAL OF CLINICAL ONCOLOGY

Determining the Best Dose for the Individual Patient

(2011) Ron H.J. Mathijssen et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non–Small-Cell Lung Cancer

(2011) Suresh S. Ramalingam et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer

(2011) Lecia V. Sequist et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors

(2011) Timothy A. Yap et al.   JOURNAL OF CLINICAL ONCOLOGY

Cancer genomics: from discovery science to personalized medicine

(2011) Lynda Chin et al.   NATURE MEDICINE

The changing therapeutic landscape of castration-resistant prostate cancer

(2011) Timothy A. Yap et al.   Nature Reviews Clinical Oncology

Abiraterone and Increased Survival in Metastatic Prostate Cancer

(2011) Johann S. de Bono et al.   NEW ENGLAND JOURNAL OF MEDICINE

Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

(2011) José Baselga et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer

(2011) José Baselga et al.   NEW ENGLAND JOURNAL OF MEDICINE

Resistance to MEK Inhibitors: Should We Co-Target Upstream?

(2011) P. I. Poulikakos et al.   Science Signaling

Practical modifications to the time-to-event continual reassessment method for phase I cancer trials with fast patient accrual and late-onset toxicities

(2011) Mei-Yin C. Polley   STATISTICS IN MEDICINE

Utilizing circulating tumor cells: challenges and pitfalls

(2010) Gerhardt Attard et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Epidermal growth factor receptor inhibitors in oncology

(2010) Igor Vivanco et al.   CURRENT OPINION IN ONCOLOGY

Review of Draft FDA Adaptive Design Guidance

(2010) Thomas Cook et al.   Journal of Biopharmaceutical Statistics

Clinical Implications of the Cancer Genome

(2010) Laura E. MacConaill et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I Studies of Drug Combinations

(2010) Jaap Verweij et al.   JOURNAL OF CLINICAL ONCOLOGY

Targeting the HGF/c-Met Axis: State of Play

(2010) T. A. Yap et al.   MOLECULAR CANCER THERAPEUTICS

Translating cancer research into targeted therapeutics

(2010) J. S. de Bono et al.   NATURE

Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements

(2010) Shivanni Kummar et al.   NATURE REVIEWS DRUG DISCOVERY

Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

(2010) Eunice L. Kwak et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inhibition of Mutated, Activated BRAF in Metastatic Melanoma

(2010) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combining Targeted Therapies: Practical Issues to Consider at the Bench and Bedside

(2010) J. Rodon et al.   ONCOLOGIST

Novel Agents on the Horizon for Cancer Therapy

(2009) W. W. Ma et al.   CA-A CANCER JOURNAL FOR CLINICIANS

PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers

(2009) S. Wee et al.   CANCER RESEARCH

Phase I Drug Combination Trial Design: Walking the Tightrope

(2009) Paul Hamberg et al.   JOURNAL OF CLINICAL ONCOLOGY

Predictors of Primary Imatinib Resistance in Chronic Myelogenous Leukemia Are Distinct From Those in Secondary Imatinib Resistance

(2009) Wenyong W. Zhang et al.   JOURNAL OF CLINICAL ONCOLOGY

Inhibition of Poly(ADP-Ribose) Polymerase in Tumors fromBRCAMutation Carriers

(2009) Peter C. Fong et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting the PI3K–AKT–mTOR pathway: progress, pitfalls, and promises

(2008) Timothy A Yap et al.   CURRENT OPINION IN PHARMACOLOGY

Optimising the design of phase II oncology trials: The importance of randomisation

(2008) Mark J. Ratain et al.   EUROPEAN JOURNAL OF CANCER

The PTEN–PI3K pathway: of feedbacks and cross-talks

(2008) A Carracedo et al.   ONCOGENE