Farmacologia degli inibitori TK e mtor

Size: px
Start display at page:

Download "Farmacologia degli inibitori TK e mtor"

Transcription

1 Farmacologia degli inibitori TK e mtor Romano Danesi Professore ordinario di Farmacologia UOC Farmacologia Universitaria Azienda Ospedaliero-Universitaria Pisana Dipartimento di Medicina Interna Università di Pisa Farmacologia inibitori TKI e mtor 1

2 The TKI dilemma: antiangiogenic vs. global inhibitors Farmacologia inibitori TKI e mtor 2

3 Common pharmacologic questions on TKI Do TKI differ by affinity, potency, specificity? What are the determinants of potency? Is selectivity a therapeutic advantage? Farmacologia inibitori TKI e mtor 3

4 Key definitions: drug-target interactions k 1 D + R DR Complex Effect k 2 Drug-receptor binding is transient and reversible k 1 - Rate at which drug associates with receptor k 2 - Rate at which drug dissociates from receptor Farmacologia inibitori TKI e mtor 4

5 Key definitions: drug-target affinity k 1 D + R DR Complex Effect k 2 Affinity is a quantitative measure of the attraction between drug molecules and receptors Kd or dissociation constant is a measure of drug affinity for a specific receptor Affinity can be determined as: Kd = k 2 /k 1 Farmacologia inibitori TKI e mtor 5

6 To summarize Drug High affinity Target Drug Low affinity Target Selective interaction Drug Non-selective interaction Drug Target Target Farmacologia inibitori TKI e mtor 6

7 Key definitions: drug potency is the dose necessary to produce a given effect Factors affecting drug potency: Accessibility (Pharmacokinetics) Affinity (Pharmacodynamics) Intrinsic activity (Pharmacodynamics) Farmacologia inibitori TKI e mtor 7

8 IC50 values of pazopanib, sunitinib, and sorafenib against kinases Kumar R et al. British Journal of Cancer (2009) 101, Farmacologia inibitori TKI e mtor 8

9 Half maximal inhibitory concentration (IC50: nmol/l) of TKI for receptor tyrosine kinases VEGFR1 VEGFR2 VEGFR3 c-kit PDGFRα PDGFRβ Axitinib Sunitinib Sorafenib Pazopanib Goldstein R et al. Expert Rev Anticancer Ther 2010; 10(10): Farmacologia inibitori TKI e mtor 9

10 Relative potencies and selectivities of VEGFR TKIs Farmacologia inibitori TKI e mtor 10

11 What is the role of Flt-3 in RCC immunity? Flt-3 suppression may restore, at least in part, immune response by suppressing T- reg and myeloid-suppressor cells Farmacologia inibitori TKI e mtor 11

12 What is the role of PDGF in resistance to VEGF inhibitors? 1 Oromi A et al Cell Du R Cancer Cell Ebos JM et al PNAS 2007 SDF1α CAFs Osteopontin PDGF BMDCs MMP9 SDF1α Adapted from Casanovas O Cancer Cell 2005 Bone marrow derived cells (i.e myeloid suppressive cells) Cancer associated fibroblasts R. Danesi Farmacologia inibitori TKI e mtor 12

13 Does selectivity turn into a therapeutic advantage or not? Farmacologia inibitori TKI e mtor 13

14 Farmacologia inibitori TKI e mtor 14

15 Effect of TKI on cellular kinases Farmacologia inibitori TKI e mtor 15

16 Effect of TKI on cellular kinases Pazopanib Farmacologia inibitori TKI e mtor 16

17 Are all multi-targeted tyrosine kinase inhibitors created equal? An in vitro study of sunitinib and pazopanib in renal cell carcinoma cell lines Daniel Canter, MD, Alexander Kutikov, MD, Konstantin Golovine, MD, Petr Makhov, MD, Jay Simhan, MD, Robert G. Uzzo, MD, Vladimir M. Kolenko, MD Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA The Canadian Journal of Ur ology ; 18(4); August 2011 Farmacologia inibitori TKI e mtor 17

18 Effect of sunitinib and pazopanib on proliferation of human renal carcinoma cells Farmacologia inibitori TKI e mtor 18

19 Effect of sunitinib and pazopanib on apoptosis of human renal carcinoma cells Farmacologia inibitori TKI e mtor 19

20 The role of rapalogs in the treatment of cancer Farmacologia inibitori TKI e mtor 20

21 Inhibition of the PI3K/AKT/mTOR pathway Schatz JH. Curr Oncol Rep (2011) 13: Farmacologia inibitori TKI e mtor 21

22 Chemical structures of rapamycin analogs in oncology clinical trials Boni JP. Semin Oncology, 36 (6, Suppl 3):2009, S18-S25 Farmacologia inibitori TKI e mtor 22

23 Mean plasma concentrations of CCI-779 (solid) and sirolimus following intravenous doses Raymond E, et al. J Clin Oncol 22: , 2004 CCI-779 displayed no immunosuppressive effects with manageable and reversible adverse events at doses up to 220 mg/m 2, the highest dose tested. Farmacologia inibitori TKI e mtor 23

24 Measurement of mtor/p-s6rp inhibition in healthy subjects following treatment with IV temsirolimus Fraction of Base eline Response CD3+ PBMCs Time (hours) Temsirolimus Dose 1 mg 3 mg 10 mg 15 mg 25 mg Boni JP. Semin Oncology, 36 (6, Suppl 3):2009, S18-S25 Farmacologia inibitori TKI e mtor 24

25 Relationship between proportional decrement in p70s6 kinase activity and time to tumor progression Peralba JM et al. Clin Cancer Res 2003;9: Farmacologia inibitori TKI e mtor 25

26 Effect of temsirolimus on Akt (Ser473) and ps6 phosphorylation in the Jeko1 MCL cell line Younes A, Autophagy 4 (5): , 2008 Farmacologia inibitori TKI e mtor 26

27 Mechanisms of rapalog resistance Nawrocki ST et al. Targ Oncol (2011) 6:17 27 Farmacologia inibitori TKI e mtor 27

28 Conclusions An enhanced potency of TKI inhibitors may overcome the limitations of drug distribution associated with tumor vascularization. The ability to inhibit PDGF may be important because the development of resistance to angiogenesis inhibitors may be due to upregulation of VEGF alternative pathways. Overall biologic efficacy may be enhanced by broadening the targets of kinase inhibition. Inhibition of mtor signaling is better defined within PK/PD models. The FKBP12-independent effect could be directly related to the antitumor activities of rapalogues in cancer patients independent of immune suppression. Farmacologia inibitori TKI e mtor 28

PROSPETTIVE FUTURE NEL TRATTAMENTO. Cinzia Ortega Dipartimento di Oncologia Medica Fondazione del Piemonte per l Oncologia I.R.C.C.S.

PROSPETTIVE FUTURE NEL TRATTAMENTO. Cinzia Ortega Dipartimento di Oncologia Medica Fondazione del Piemonte per l Oncologia I.R.C.C.S. PROSPETTIVE FUTURE NEL TRATTAMENTO MEDICO DEL mrcc Cinzia Ortega Dipartimento di Oncologia Medica Fondazione del Piemonte per l Oncologia I.R.C.C.S. Candiolo Future strategies in mrcc Improve therapeutic

More information

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals

What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals What is New in Oncology Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals Personalized Medicine Personalized Genomics Genomic Medicine Precision Medicine Definition Application

More information

GENETIC PROFILES AND TARGETED TREATMENT OF CANCER - PERSONALIZED MEDICINE

GENETIC PROFILES AND TARGETED TREATMENT OF CANCER - PERSONALIZED MEDICINE GENETIC PROFILES AND TARGETED TREATMENT OF CANCER - PERSONALIZED MEDICINE Branko Zakotnik MD, PhD Department of Medical Oncology Institute of Oncology Ljubljana 1 I have no conflict of interest to declare

More information

CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR)

CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR) CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR) This late-breaking abstract was presented on 26 th September 215 in Presidential

More information

Precision oncology: identifying predictive biomarkers for the treatment of metastatic renal cell carcinoma

Precision oncology: identifying predictive biomarkers for the treatment of metastatic renal cell carcinoma Perspective Precision oncology: identifying predictive biomarkers for the treatment of metastatic renal cell carcinoma Parth K. Modi 1, Nicholas J. Farber 1, Eric A. Singer 1,2 1 Division of Urology, Rutgers

More information

FARMACI PERSONALIZZATI PER

FARMACI PERSONALIZZATI PER ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI FONDAZIONE G. Pascale NAPOLI SC Biologia Cellulare e Bioterapie CENTRO RICERCHE ONCOLOGICHE MERCOGLIANO (AV) Laboratorio di Farmacogenomica FARMACI

More information

Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma

Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma g Tumor Res. Basel, Karger, 2014, vol 41, pp 98 112 (DOI: 10.1159/000355906) Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma Marc Pracht Dominik Berthold Medical Oncology Unit,

More information

Drug treatments for kidney cancer

Drug treatments for kidney cancer James Whale Fund for Kidney Cancer Drug treatments for kidney cancer Before your doctors can discuss treatment options with you they need to know how far your cancer has progressed. Staging is used to

More information

ASCO Initiatives in Personalized Medicine. Richard L. Schilsky, MD, FACP, FASCO Chief Medical Officer American Society of Clinical Oncology

ASCO Initiatives in Personalized Medicine. Richard L. Schilsky, MD, FACP, FASCO Chief Medical Officer American Society of Clinical Oncology ASCO Initiatives in Personalized Medicine Richard L. Schilsky, MD, FACP, FASCO Chief Medical Officer American Society of Clinical Oncology Financial Disclosures No financial relationships to disclose.

More information

1/17/2013. Dose Response and Concentration Response Analysis of Drug Effects

1/17/2013. Dose Response and Concentration Response Analysis of Drug Effects Dose Response and Concentration Response Analysis of Drug Effects Juan J. L. Lertora. M.D., Ph.D. IH Clinical Center January 17, 213 1 DOSE-EFFECT RELATIOSHIP The intensity and duration of a drug s effect(s)

More information

NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy S-1 NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy Gary R. Hudes, MD; Michael A. Carducci, MD; Toni K. Choueiri, MD; Peg Esper, MSN, MSA,

More information

LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials

LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials LEUKEMIA LYMPHOMA MYELOMA Advances in Clinical Trials OUR FOCUS ABOUT emerging treatments Presentation for: Judith E. Karp, MD Advancements for Acute Myelogenous Leukemia Supported by an unrestricted educational

More information

Cancercare Connect Booklet Series. Renal Cell Cancer. www.cancercare.org

Cancercare Connect Booklet Series. Renal Cell Cancer. www.cancercare.org Cancercare Connect Booklet Series Treatment Update Renal Cell Cancer www.cancercare.org Treatment Update Renal Cell Cancer Table of Contents The CancerCare Connect Booklet Series offers up-to-date, easy-to-read

More information

Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics

Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics EPAAC WP8 Research Forum - 2 July, Sofitel Hotel Europe, Brussels Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics JY Blay, Past President EORTC

More information

Sorafenib. Bernard ESCUDIER Institut Gustave Roussy Villejuif, France

Sorafenib. Bernard ESCUDIER Institut Gustave Roussy Villejuif, France Sorafenib for renal cell carcinoma Bernard ESCUDIER Institut Gustave Roussy Villejuif, France Renal Cell Carcinoma: Drugs and Targets pvhl = HIFα CCI-779 Bevacizumab VEGF KDR PDGF PDGFR TGFα EGFR Sunitinib,

More information

treatments) worked by killing cancerous cells using chemo or radiotherapy. While these techniques can

treatments) worked by killing cancerous cells using chemo or radiotherapy. While these techniques can Shristi Pandey Genomics and Medicine Winter 2011 Prof. Doug Brutlag Chronic Myeloid Leukemia: A look into how genomics is changing the way we treat Cancer. Until the late 1990s, nearly all treatment methods

More information

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.

More information

Ganetespib and Docetaxel in NSCLC

Ganetespib and Docetaxel in NSCLC Ganetespib and Docetaxel in NSCLC Suresh S. Ramalingam, MD Associate Professor Director, Division of Medical Oncology Emory University Winship Cancer Institute 1 Role of Docetaxel in Advanced NSCLC Docetaxel

More information

Exelixis Showcases R&D Pipeline at JPMorgan Healthcare Conference

Exelixis Showcases R&D Pipeline at JPMorgan Healthcare Conference Exelixis Showcases R&D Pipeline at JPMorgan Healthcare Conference Two New Clinical Programs and Significant Expansion of Cancer Pipeline Planned for 2004 SOUTH SAN FRANCISCO, Calif., Jan. 13 /PRNewswire-FirstCall/

More information

Background. t 1/2 of 3.7 4.7 days allows once-daily dosing (1.5 mg) with consistent serum concentration 2,3 No interaction with CYP3A4 inhibitors 4

Background. t 1/2 of 3.7 4.7 days allows once-daily dosing (1.5 mg) with consistent serum concentration 2,3 No interaction with CYP3A4 inhibitors 4 Abstract No. 4501 Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a Phase III randomized, open-label, multicenter trial R. Motzer, D.

More information

DOSE-EFFECT RELATIONSHIP

DOSE-EFFECT RELATIONSHIP DOSE-EFFECT RELATIONSHIP A fundamental principle of pharmacology is that the intensity of effect produced by a drug is a function of the quantity of drug administered (or the concentration of the drug

More information

Preliminary Results from a Phase 2 Study of ARQ 197 in Patients with Microphthalmia Transcription Factor Family (MiT) Associated Tumors

Preliminary Results from a Phase 2 Study of ARQ 197 in Patients with Microphthalmia Transcription Factor Family (MiT) Associated Tumors Preliminary Results from a Phase 2 Study of ARQ 197 in Patients with Microphthalmia Transcription Factor Family (MiT) Associated Tumors John Goldberg 1 *, George Demetri 2, Edwin Choy 3, Lee Rosen 4, Alberto

More information

Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms

Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms Wolfram Samlowski, MD For a CME/CEU version of this article please go to www.namcp.org/cmeonline.htm, and then

More information

a Phase 2 prostate cancer clinical trial is ongoing. Table 2: Squalamine vs Standard-of-care literature

a Phase 2 prostate cancer clinical trial is ongoing. Table 2: Squalamine vs Standard-of-care literature PRODUCT FACT SHEET Spring 2007 MISSION STATEMENT Genaera Corporation is a biopharmaceutical company with a focus on metabolic and respiratory diseases. The compounds in the Genaera pipeline address signal

More information

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors Drug Monitoring Symposium Swiss MedLab 2012 Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors Nicolas Widmer, PharmD, PhD Division of Clinical Pharmacology Centre Hospitalier Universitaire Vaudois

More information

Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta

Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta S.C. di Oncologia Medica, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia Non-Clear Cell Renal Cell Carcinoma (nccrcc) nccrcc

More information

THE CANCER STEM CELL INHIBITORS VS-6063 AND VS-5584 EXHIBIT SYNERGISTIC ANTICANCER ACTIVITY IN PRECLINICAL MODELS OF MESOTHELIOMA

THE CANCER STEM CELL INHIBITORS VS-6063 AND VS-5584 EXHIBIT SYNERGISTIC ANTICANCER ACTIVITY IN PRECLINICAL MODELS OF MESOTHELIOMA THE CANCER STEM CELL INHIBITORS VS-6063 AND VS-5584 EXHIBIT SYNERGISTIC ANTICANCER ACTIVITY IN PRECLINICAL MODELS OF MESOTHELIOMA Mitchell Keegan, Ph.D. Vice President of Development, Verastem, Inc. 1

More information

FAK INHIBITOR DEFACTINIB (VS-6063) TARGETS MESOTHELIOMA CANCER STEM CELLS. Jonathan Pachter, Ph.D.

FAK INHIBITOR DEFACTINIB (VS-6063) TARGETS MESOTHELIOMA CANCER STEM CELLS. Jonathan Pachter, Ph.D. FAK INHIBITOR DEFACTINIB (VS-6063) TARGETS MESOTHELIOMA CANCER STEM CELLS Rationale for maintenance therapy after conventional therapy Jonathan Pachter, Ph.D. Vice President of Research, Verastem, Inc.

More information

Adaptive capabilities of the PI3K/Akt/mTOR axis in Acute Myeloid Leukemia revealed by pathway selective inhibition and phosphoproteome analysis

Adaptive capabilities of the PI3K/Akt/mTOR axis in Acute Myeloid Leukemia revealed by pathway selective inhibition and phosphoproteome analysis Adaptive capabilities of the PI3K/Akt/mTOR axis in Acute Myeloid Leukemia revealed by pathway selective inhibition and phosphoproteome analysis University of Padova University of Modena and Reggio Emilia

More information

What is the Optimal Front-Line Treatment for mrcc? Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center

What is the Optimal Front-Line Treatment for mrcc? Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center What is the Optimal Front-Line Treatment for mrcc? Michael B. Atkins, MD Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center The Case for Immunotherapy in mrcc 1. Achieves patient s goal 2.

More information

A disease of populations of cells that live, divide, invade and spread without regard to normal limits

A disease of populations of cells that live, divide, invade and spread without regard to normal limits 1 Targeted Cancer Therapies Mark McKeage Medical Oncology Specialist Professor in Clinical Pharmacology 2 Cancer Definition- A disease of populations of cells that live, divide, invade and spread without

More information

Signaling monitoring and flow cytometry

Signaling monitoring and flow cytometry Signaling monitoring and flow cytometry Coultry Club, FIAP Paris April 8, 2014 Dr Jacques Nunès Lymphocyte Activation Group 1 PLAN I Signalisation intracellulaire & «signal monitoring» II Méthodologie

More information

Critical Pathways Forward in the Treatment of Renal Cell Carcinoma

Critical Pathways Forward in the Treatment of Renal Cell Carcinoma Critical Pathways Forward in the Treatment of Renal Cell Carcinoma Based on an Expert Summit convened in Washington, DC, July 30-31, 2012 Key Points 1. The approval of seven agents, all targeting angiogenesis,

More information

The New Kid on the Block for Advanced Renal Cell Carcinoma

The New Kid on the Block for Advanced Renal Cell Carcinoma The New Kid on the Block for Advanced Renal Cell Carcinoma Wyeth Pharmaceuticals recently launched Torisel (temsirolimus), a targeted, first-in-class mtor inhibitor. This new treatment for metastatic renal

More information

Histopathology and prognosis in renal cancer

Histopathology and prognosis in renal cancer Histopathology and prognosis in renal cancer Granular cell Granular cell Granular cell Granular cell Clear cell Chromophobe cell Papillary type 2 Luca Mazzucchelli Istituto cantonale di patologia, Locarno

More information

Renal Cell Carcinoma (Event Driven)

Renal Cell Carcinoma (Event Driven) Brochure More information from http://www.researchandmarkets.com/reports/2365661/ Renal Cell Carcinoma (Event Driven) Description: The Renal Cell Carcinoma market is highly lucrative. We anticipate that

More information

Stage IV Renal Cell Carcinoma. Changing Management in A Comprehensive Community Cancer Center. Susquehanna Health Cancer Center

Stage IV Renal Cell Carcinoma. Changing Management in A Comprehensive Community Cancer Center. Susquehanna Health Cancer Center Stage IV Renal Cell Carcinoma Changing Management in A Comprehensive Community Cancer Center Susquehanna Health Cancer Center 2000 2009 Warren L. Robinson, MD, FACP January 27, 2014 Introduction 65,150

More information

MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION

MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION Nadia Terranova UNIVERSITÀ DI PAVIA New model development: course of action

More information

Paris-Sud / CSC program 2014 PhD project proposal form. Discipline Chemistry

Paris-Sud / CSC program 2014 PhD project proposal form. Discipline Chemistry Paris-Sud / CSC program 2014 PhD project proposal form Please convert this file to PDF format before uploading it to http://www.u-psud.fr/csc/ Discipline Chemistry Doctoral School 425 - Therapeutic Innovations:

More information

Cellular, Molecular, and Biochemical Targets in Breast Cancer

Cellular, Molecular, and Biochemical Targets in Breast Cancer Cellular, Molecular, and Biochemical Targets in Breast Cancer Kristy Kummerow Ingrid Meszoely December 12, 2012 VUMC Resident Bonus Conference One size fits all surgical treatment of breast cancer Wilhelm

More information

Title: Making Optimal Therapeutic Decisions in Patients with Advanced Renal Cell Carcinoma

Title: Making Optimal Therapeutic Decisions in Patients with Advanced Renal Cell Carcinoma Overall Aim and Objectives: Program Synopsis Title: Making Optimal Therapeutic Decisions in Patients with Advanced Renal Cell Carcinoma Clinical Synopsis: New options for targeted treatment of metastatic

More information

BNC105 CANCER CLINICAL TRIALS REACH KEY MILESTONES CLINICAL PROGRAM TO BE EXPANDED

BNC105 CANCER CLINICAL TRIALS REACH KEY MILESTONES CLINICAL PROGRAM TO BE EXPANDED ASX ANNOUNCEMENT 3 August 2011 ABN 53 075 582 740 BNC105 CANCER CLINICAL TRIALS REACH KEY MILESTONES CLINICAL PROGRAM TO BE EXPANDED Data from renal cancer trial supports progression of the trial: o Combination

More information

BNC105 PHASE II RENAL CANCER TRIAL RESULTS

BNC105 PHASE II RENAL CANCER TRIAL RESULTS ABN 53 075 582 740 ASX ANNOUNCEMENT 19 March 2014 BNC105 PHASE II RENAL CANCER TRIAL RESULTS Results show BNC105 utility in patients with advanced disease Identified biomarkers which correlate with patient

More information

Multiple Myeloma (Event Driven)

Multiple Myeloma (Event Driven) Brochure More information from http://www.researchandmarkets.com/reports/2234830/ Multiple Myeloma (Event Driven) Description: The 2010 multiple myeloma (myeloma) market garnered impressive sales despite

More information

Clinical Management Guideline Management of locally advanced or recurrent Renal cell carcinoma. Protocol for Planning and Treatment

Clinical Management Guideline Management of locally advanced or recurrent Renal cell carcinoma. Protocol for Planning and Treatment Protocol for Planning and Treatment The process to be followed in the management of: LOCALLY ADVANCED OR METASTATIC RENAL CELL CARCINOMA Patient information given at each stage following agreed information

More information

Guidance for Industry

Guidance for Industry Guidance for Industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center

More information

Health Insurance and Cancer Drug Reimbursement

Health Insurance and Cancer Drug Reimbursement Quality health plans & benefits Healthier living Financial well-being Intelligent solutions Health Insurance and Cancer Drug Reimbursement Michael Kolodziej, M.D., FACP National Medical Director, Oncology

More information

Pharmacogenomic markers in EGFR-targeted therapy of lung cancer

Pharmacogenomic markers in EGFR-targeted therapy of lung cancer Pharmacogenomic markers in EGFR-targeted therapy of lung cancer Rafal Dziadziuszko, MD, PhD University of Colorado Cancer Center, Aurora, CO, USA Medical University of Gdansk, Poland EMEA Workshop on Biomarkers,

More information

Myeloid Leukemias - Current and Future Approaches to Targeted and Individualized Therapies

Myeloid Leukemias - Current and Future Approaches to Targeted and Individualized Therapies Myeloid Leukemias - Current and Future Approaches to Targeted and Individualized Therapies Robert J. Arceci, M.D., Ph.D. King Fahd Professor of Pediatric Oncology Professor of Pediatrics, Oncology and

More information

Avastin (Renal Cell Carcinoma) - Analysis and Forecasts to 2022

Avastin (Renal Cell Carcinoma) - Analysis and Forecasts to 2022 Brochure More information from http://www.researchandmarkets.com/reports/2228475/ Avastin (Renal Cell Carcinoma) - Analysis and Forecasts to 2022 Description: Avastin (Renal Cell Carcinoma) Analysis and

More information

Come valutare la risposta o la progressione nei pazienti in trattamento con terapie biologiche

Come valutare la risposta o la progressione nei pazienti in trattamento con terapie biologiche Come valutare la risposta o la progressione nei pazienti in trattamento con terapie biologiche Andrea Busolo U.O. di Radiologia Rocco De Vivo U.O. di Oncologia Medica ULSS 6 - Vicenza Activity and efficacy

More information

Meccanismi di resistenza all inibizione della via di segnale PI3K/Akt/mTOR nella LAM

Meccanismi di resistenza all inibizione della via di segnale PI3K/Akt/mTOR nella LAM Meccanismi di resistenza all inibizione della via di segnale PI3K/Akt/mTOR nella LAM University of Modena and Reggio Emilia Cell Signaling Unit, ChiMOMo Sandra Marmiroli Jessika Bertacchini Laura Mediani

More information

Technology Assessment Report commissioned by the NHS R&D HTA Programme on behalf of the National Institute for Health and Clinical Excellence

Technology Assessment Report commissioned by the NHS R&D HTA Programme on behalf of the National Institute for Health and Clinical Excellence Technology Assessment Report commissioned by the NHS R&D HTA Programme on behalf of the National Institute for Health and Clinical Excellence Protocol 26 October 2007 PROJECT TITLE Bevacizumab, sorafenib

More information

TECHNICAL INSIGHTS TECHNOLOGY ALERT

TECHNICAL INSIGHTS TECHNOLOGY ALERT TECHNICAL INSIGHTS TECHNOLOGY ALERT UNLOCKING BREAST CANCER TUMORS' DRUG RESISTANCE A troubling phenomenon in breast cancer treatment is that some patients tumors become resistant to treatments over time.

More information

Cytotoxic and Biotherapies Credentialing Programme Module 2

Cytotoxic and Biotherapies Credentialing Programme Module 2 Cytotoxic and Biotherapies Credentialing Programme Module 2 1. The Cell Cycle 2. Cancer Therapies 3. Adjunctive Therapies On completion of this module the RN will State the difference between a normal

More information

New systemic treatment options for radioiodinerefractory. medullary thyroid cancers

New systemic treatment options for radioiodinerefractory. medullary thyroid cancers New systemic treatment options for radioiodinerefractory differentiated and medullary thyroid cancers Prof. Dr. Patrick Schöffski, MPH, Department of General Medical Oncology University Hospitals Leuven,

More information

Dec. 9, 2013, 11:00 a.m. EST

Dec. 9, 2013, 11:00 a.m. EST Dec. 9, 2013, 11:00 a.m. EST Portola Pharmaceuticals Announces New Phase 2 Results Confirming Immediate, Dose-Dependent and Well-Tolerated Reversal of Anticoagulation Activity of XARELTO(R) (rivaroxaban)

More information

Innovations in Kidney Cancer

Innovations in Kidney Cancer Innovations in Kidney Cancer Guest Expert: Harriet, MD Associate Professor of Medical Oncology Edward, MD Assistant Professor of Surgical Urology www.wnpr.org www.yalecancercenter.org Welcome to Yale Cancer

More information

Monoclonal Antibodies in Cancer. Ralph Schwall, PhD Associate Director, Translational Oncology Genentech, Inc.

Monoclonal Antibodies in Cancer. Ralph Schwall, PhD Associate Director, Translational Oncology Genentech, Inc. Monoclonal Antibodies in Cancer Ralph Schwall, PhD Associate Director, Translational Oncology Genentech, Inc. Disclaimer I had nothing to do with Herceptin Using lessons learned in new antibody projects

More information

Nursing 113. Pharmacology Principles

Nursing 113. Pharmacology Principles Nursing 113 Pharmacology Principles 1. The study of how drugs enter the body, reach the site of action, and are removed from the body is called a. pharmacotherapeutics b. pharmacology c. pharmacodynamics

More information

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

More information

(Chin J New Drugs Clin Rem),2015 9, )

(Chin J New Drugs Clin Rem),2015 9, ) 692 [ ]1007-7669(2015)09-0692-05 [DOI ]10.14109/j.cnki.xyylc.2015.09.012 Ziv- 宋 敏 (, 361004) [ ] Ziv- ; ;, [ ] (mcrc) 2012 Ziv- mcrc, Ziv-, (VEGF), Ziv- mcrc, Ziv- mcrc [ ] R979.1 [ ] A Progression of

More information

Miquel Àngel Seguí Palmer

Miquel Àngel Seguí Palmer Miquel Àngel Seguí Palmer HER2+ Breast Cancer is characterized by overexpression of HER2 receptors HER2+ Breast Cancer is characterized by overexpression of HER2 receptors HER2+ status is associated with

More information

Anti-angiogenesis Treatment

Anti-angiogenesis Treatment Anti-angiogenesis Treatment The search for better cancer drugs Today we are better able to treat cancer than ever. More than half of all people with cancer now live at least 5 years after being diagnosed.

More information

EU Media Inquiries: Satu Kaarina Glawe Phone: +49 (0) 2638 947 9218 Mobile: +49 (172) 294 6264 Email: sglawe@its.jnj.com

EU Media Inquiries: Satu Kaarina Glawe Phone: +49 (0) 2638 947 9218 Mobile: +49 (172) 294 6264 Email: sglawe@its.jnj.com EU Media Inquiries: Satu Kaarina Glawe Phone: +49 (0) 2638 947 9218 Mobile: +49 (172) 294 6264 Email: sglawe@its.jnj.com Investor Relations: Stan Panasewicz Phone: +1 732-524-2524 Louise Mehrotra Phone:

More information

Targeted Therapy What the Surgeon Needs to Know

Targeted Therapy What the Surgeon Needs to Know Targeted Therapy What the Surgeon Needs to Know AATS Focus in Thoracic Surgery 2014 David R. Jones, M.D. Professor & Chief, Thoracic Surgery Memorial Sloan Kettering Cancer Center I have no disclosures

More information

NEW BIOACTIVE PRODUCTS. B-RAF Inhibitors

NEW BIOACTIVE PRODUCTS. B-RAF Inhibitors B-RAF Inhibitors BAM66400 CHF 5074, 96+% 1mg: $300 A novel, potent and selective small molecule B-Raf kinase BAM66393 GDC-0879, BAM66396 PLX-4032 (RG7204/Vemurafenib/Zelboraf), 96+% BAM66397 PLX-4720,

More information

INTRODUCTION % Cells of Control % Cells of Control % Cells of Control A B Rapamycin 24 Hour 48 Hour MS-275 24 Hour 48 Hour 120.000 120.000 100.000 100.000 80.000 80.000 60.000 60.000 40.000 40.000

More information

Cancer and the immune system: can we beat cancer at its own game?

Cancer and the immune system: can we beat cancer at its own game? Cancer and the immune system: can we beat cancer at its own game? Andrew R. Haas, MD, PhD Assistant Professor of Medicine University of Pennsylvania Medical Center Philadelphia, Pa Why can t immune

More information

Comparing Immunotherapy with High Dose IL-2 and Ipilimumab

Comparing Immunotherapy with High Dose IL-2 and Ipilimumab Comparing Immunotherapy with High Dose IL-2 and Ipilimumab Michael K Wong MD PhD FRCPC mike.wong@med.usc.edu Disclosures Speaker s Bureau, Advisory Boards, Consultant: Prometheus Bristol Myers Squibb Novartis

More information

Novel Oral Anti-coagulants in Patients with Malignancy Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC McMaster University, Hamilton, ON

Novel Oral Anti-coagulants in Patients with Malignancy Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC McMaster University, Hamilton, ON Novel Oral Anti-coagulants in Patients with Malignancy Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC McMaster University, Hamilton, ON Disclosures Speaker honorarium from Bayer (rivaroxaban; Xarelto) and

More information

Brigham and Women s Hospital, Boston, MA, USA; 2 Verastem, Inc., Boston, MA, USA

Brigham and Women s Hospital, Boston, MA, USA; 2 Verastem, Inc., Boston, MA, USA Determination of Biomarker Response in a Phase II Window of Opportunity Study of Defactinib (VS 6063), a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with Resectable Malignant Pleural Mesothelioma

More information

Notch 1 -dependent regulation of cell fate in colorectal cancer

Notch 1 -dependent regulation of cell fate in colorectal cancer Notch 1 -dependent regulation of cell fate in colorectal cancer Referees: PD Dr. Tobias Dick Prof. Dr. Wilfried Roth http://d-nb.info/1057851272 CONTENTS Summary 1 Zusammenfassung 2 1 INTRODUCTION 3 1.1

More information

Post-operative intrapleural chemotherapy for mesothelioma

Post-operative intrapleural chemotherapy for mesothelioma Post-operative intrapleural chemotherapy for mesothelioma Robert Kratzke, MD John Skoglund Chair for Lung Cancer Research Section of Heme-Onc-Transplant University of Minnesota Medical School Efficacy

More information

Metastatic Breast Cancer 201. Carolyn B. Hendricks, MD October 29, 2011

Metastatic Breast Cancer 201. Carolyn B. Hendricks, MD October 29, 2011 Metastatic Breast Cancer 201 Carolyn B. Hendricks, MD October 29, 2011 Overview Is rebiopsy necessary at the time of recurrence or progression of disease? How dose a very aggressive treatment upfront compare

More information

New Directions in Treatment of Ovarian Cancer. Amit M. Oza Princess Margaret Hospital University of Toronto

New Directions in Treatment of Ovarian Cancer. Amit M. Oza Princess Margaret Hospital University of Toronto New Directions in Treatment of Ovarian Cancer Amit M. Oza Princess Margaret Hospital University of Toronto Newly diagnosed: scenario Ist line Surgery chemotherapy Cure If can t cure can we turn into chronic

More information

CLINICAL POLICY Department: Medical Management Document Name: Opdivo Reference Number: CP.PHAR.121 Effective Date: 07/15

CLINICAL POLICY Department: Medical Management Document Name: Opdivo Reference Number: CP.PHAR.121 Effective Date: 07/15 Page: 1 of 6 IMPORTANT REMINDER This Clinical Policy has been developed by appropriately experienced and licensed health care professionals based on a thorough review and consideration of generally accepted

More information

I've Just Been Diagnosed. with Kidney Cancer: What s Next?

I've Just Been Diagnosed. with Kidney Cancer: What s Next? I've Just Been Diagnosed with Cancer: What s Next? Table of Contents Introduction Message from a Survivor What are the s and What is Their Function? What is Cancer? What are the Types of Cancer? What are

More information

Clinical Trial Results Database Page 1

Clinical Trial Results Database Page 1 Clinical Trial Results Database Page Sponsor Novartis Generic Drug Name BGT6 Therapeutic Area of Trial Advanced solid malignancies Approved Indication Investigational Study Number CBGT6A0 Title A phase

More information

Sarcoma Research Group Group leader: Òscar Martínez Tirado

Sarcoma Research Group Group leader: Òscar Martínez Tirado Sarcoma Research Group Group leader: Òscar Martínez Tirado IDIBELL since 2007 Miguel Servet program (Fondo de Investigaciones Sanitarias) 2009 Sarcoma Research Group (SGR682) Group leader: Òscar Martínez

More information

Course Curriculum for Master Degree in Clinical Pharmacy

Course Curriculum for Master Degree in Clinical Pharmacy Course Curriculum for Master Degree in Clinical Pharmacy The Master Degree in Clinical Pharmacy is awarded by the Faculty of Graduate studies at Jordan University of Science and Technology (JUST) upon

More information

Cancer treatment and diabetes

Cancer treatment and diabetes Cancer treatment and diabetes Dr Daniel Morganstein Consultant Endocrinologist, 1 2 Diabetes and cancer Cancer and its treatment also poses challenges to managing diabetes Surgery Altered appetite Cachexia

More information

New anticoagulants: Monitoring or not Monitoring? Not Monitoring

New anticoagulants: Monitoring or not Monitoring? Not Monitoring The 2 nd World Congress on CONTROVERSIES IN HEMATOLOGY (COHEM) Barcelona, Spain September 6 8, 2012 New anticoagulants: Monitoring or not Monitoring? Not Monitoring Anna Falanga, MD Immunohematology and

More information

PI3K signaling pathway a new target for breast cancer treatment

PI3K signaling pathway a new target for breast cancer treatment PI3K signaling pathway a new target for breast cancer treatment Introduction At the 37 th annual San Antonio Breast Cancer Symposium, SABCS, a number of interesting research trends, novelties as well as

More information

Classical drug resistance in the molecular age

Classical drug resistance in the molecular age Classical drug resistance in the molecular age Robert O Connor, Ph.D. Senior Programme Leader, Translational Cancer Pharmacology Lecturer in Biological Sciences, School of Nursing Chair ICORG Translational

More information

NCT Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety,

NCT Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety, NCT02020291 Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles of Foxy-5 in Patients with Metastatic Breast, Colon or Prostate

More information

Pharmacology skills for drug discovery. Why is pharmacology important?

Pharmacology skills for drug discovery. Why is pharmacology important? skills for drug discovery Why is pharmacology important?, the science underlying the interaction between chemicals and living systems, emerged as a distinct discipline allied to medicine in the mid-19th

More information

CNIO Frontiers Meetings Molecular Cancer Therapeutics Madrid, March 8 10, 2010

CNIO Frontiers Meetings Molecular Cancer Therapeutics Madrid, March 8 10, 2010 CNIO Frontiers Meetings Molecular Cancer Therapeutics Madrid, March 8 10, 2010 Organisers S. Gail Eckhardt, University of Colorado Denver, Aurora, USA Roy S. Herbst, The University of Texas MD Anderson

More information

Clinical Trials for Patients with

Clinical Trials for Patients with Clinical Trials for Patients with Malignant Pleural Mesothelioma Lee M. Krug, M.D. Memorial Sloan-Kettering Cancer Center New York, New York Challenges in MPM Clinical Trials Mesothelioma is a rare disease,

More information

Lung Cancer Research: From Prevention to Cure!

Lung Cancer Research: From Prevention to Cure! Lung Cancer Research: From Prevention to Cure! Ravi Salgia, M.D, Ph.D Associate Professor of Medicine Director, Thoracic Oncology Research Program Department of Medicine Section of Hematology/Oncology

More information

Molecular markers and clinical trial design parallels between oncology and rare diseases?

Molecular markers and clinical trial design parallels between oncology and rare diseases? Molecular markers and clinical trial design parallels between oncology and rare diseases?, Harriet Sommer Institute for Medical Biometry and Statistics, University of Freiburg Medical Center 6. Forum Patientennahe

More information

M. Ugolini 1,2, G. Babini 1,2, G. Baiocco 1,2, D. Cappelletti 1,2, L. Mariotti 1,2, J. Morini 1,2,3 and A. Ottolenghi 1,2

M. Ugolini 1,2, G. Babini 1,2, G. Baiocco 1,2, D. Cappelletti 1,2, L. Mariotti 1,2, J. Morini 1,2,3 and A. Ottolenghi 1,2 M. Ugolini 1,2, G. Babini 1,2, G. Baiocco 1,2, D. Cappelletti 1,2, L. Mariotti 1,2, J. Morini 1,2,3 and A. Ottolenghi 1,2 1 Department of Physics, University of Pavia, Pavia, Italy 2 Istituto Nazionale

More information

National Horizon Scanning Centre. Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer. December 2007

National Horizon Scanning Centre. Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer. December 2007 Vandetanib (Zactima) for advanced or metastatic non-small cell lung cancer December 2007 This technology summary is based on information available at the time of research and a limited literature search.

More information

Summary of Discussion on Non-clinical Pharmacology Studies on Anticancer Drugs

Summary of Discussion on Non-clinical Pharmacology Studies on Anticancer Drugs Provisional Translation (as of January 27, 2014)* November 15, 2013 Pharmaceuticals and Bio-products Subcommittees, Science Board Summary of Discussion on Non-clinical Pharmacology Studies on Anticancer

More information

A Medical Device Strategy To Inhibit HER2+ Breast Cancer Progression

A Medical Device Strategy To Inhibit HER2+ Breast Cancer Progression A Medical Device Strategy To Inhibit HER2+ Breast Cancer Progression September 27, 2011 James A. Joyce Chairman & CEO, Aethlon Medical, Inc jj@aethlonmedical.com Last week, we introduced HER2osome as a

More information

Successes and Limitations of Targeted Cancer Therapy in Lung Cancer

Successes and Limitations of Targeted Cancer Therapy in Lung Cancer Successes and Limitations of Targeted Cancer Therapy in Lung Cancer Kenichi Suda a, b Tetsuya Mitsudomi a a Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama,

More information

First-line Therapy for Renal Cell Carcinoma: Defining New Standards of Care from Phase III Trials

First-line Therapy for Renal Cell Carcinoma: Defining New Standards of Care from Phase III Trials First-line Therapy for Renal Cell Carcinoma: Defining New Standards of Care from Phase III Trials Joaquim Bellmunt University Hospital del Mar & Dana-Farber Cancer Institute/Brigham and Women s Hospital

More information

Navigating GIST. The Life Raft Group June 12, 2008

Navigating GIST. The Life Raft Group June 12, 2008 Navigating GIST Clinical Trials The Life Raft Group June 12, 2008 Some observations: Annually, only 3% of adult patients participate in cancer clinical trials. Lara et. al; Evaluation of factors affecting

More information

Zeroing in on Non-Small Cell Lung Cancer: Integrating Targeted Therapies into Practice

Zeroing in on Non-Small Cell Lung Cancer: Integrating Targeted Therapies into Practice Lung Cancer: Integrating Targeted Therapies into Practice Table of Contents Program Information... 2 Faculty Biographies... 3 Genomic Profiling of NSCLC for EGFR Inhibitors... 4 Fred R. Hirsch, MD, PhD

More information

Ovarian Cancer and Modern Immunotherapy: Regulatory Strategies for Drug Development

Ovarian Cancer and Modern Immunotherapy: Regulatory Strategies for Drug Development Ovarian Cancer and Modern Immunotherapy: Regulatory Strategies for Drug Development Sanjeeve Bala, MD, MPH Ovarian Cancer Endpoints Workshop FDA White Oak September 3, 2015 Overview Immune agents from

More information