WHENMarch 17, 2012 @ 8:00am - 5:00pm
WHERE
INFO
REGISTER
Date: Mar 17, 2012
Type: Association Events
Organizer: SABPA
Location: Institute of Americas, UCSD (
Source: SABPA
Frontiers in oncology SABPA Sci&Tech Forum 2012

Date: March 17, 2012 (Saturday) 8:30am To 3:00pm (Lunch will be provided)Location: Institute of Americas, UCSD (directions)

Registration: Closed

$20 for online registration, $10 for students and post-docs, $40 for on-site registration

 

Link to report of event by SABPA(shortReport)(longReport)

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This year’s SABPA Science & Technology Forum will focus on current frontiers in oncology. The presentations will address the emerging new trends in cancer drug development including translational research, pharmacogenetics, personalized targeted therapies, epigenetics, cancer stem cell, oncology clinical design and development of preclinical models. The meeting will also discuss the opportunities and challenges facing cancer drug development in San Diego biotech and pharmaceutical community: industry/academic collaboration; cancer clinical trials and venture funding in San Diego.

This forum has brought together leaders in academic and industry in the oncology field to ignite the exchange of ideas of how to build a stronger oncology community in San Diego.

speakers

David Cheresh, Ph.D.

Professor, associate director for translation research, Moores UCSD Cancer Center

Greg Reyes, M.D., Ph.D.

Senior Vice President, Drug Discovery, Celgene

Isan Chen, M.D.

Chief Medical Officer, Aragon

Jean Cui, Ph.D.

Associate research fellow, Pfizer

Jeremy Barton, M.D.

Vice President Precision Medicine, Pfizer

Jing Yang, Ph.D.

Assistant Professor of Pharmacology and Pediatrics, UCSD

Steve Kaldor, Ph.D.

Venture Partner at Versant Ventures, acting CEO, QuantiCell

Tannishtha Reya, Ph.D.

Professor, Department of Pharmacology, UCSD

Program

 

8:30-9:00 Registration & Breakfast
9:00-9:05 Opening Remarks Yi Liu, Ph.D., VP of drug discovery, Intellikine
9:05-9:10 Chairperson of session 1 Hua Gong,Ph.D.,Executive Director of Medical Diagnostics Premier Research Group
9:10-9:40 David Cheresh, Ph.D.Professor, associate director for translation research, Moores UCSD Cancer CenterTitle:A MEK-independent role for CRAF in mitosis, angiogenesis and tumor progression
Abstract: RAF kinases regulate cell proliferation and survival and can be mutated or dysregulated in tumors. A role for RAF in cell proliferation has been linked to its ability to activate MEK/ERK. Here, we identify a MEK-independent role for RAF in tumor growth. Specifically, in mitotic tumor and endothelial cells, CRAF becomes highly phosphorylated on serine 338 and localizes to the mitotic spindle poles from pro-metaphase until anaphase. Treatment of tumor and endothelial cells with allosteric, but not ATP-competitive RAF inhibitors prevents CRAF phosphorylation on serine 338, localization to the mitotic spindle and causes cell cycle arrest at pro-metaphase. Furthermore, we identify phospho-S338 CRAF as a potential biomarker for tumor progression, aberrant vascular proliferation and a surrogate marker for allosteric RAF blockade. Mechanistically, CRAF, but not BRAF is found in a complex with Polo-like kinase 1 at the centrosomes/spindle poles during G2/Mitosis. Indeed, allosteric or genetic inhibition of phospho-S338 CRAF impairs Plk1 activity and its accumulation at kinetochores causing pro-metaphase arrest, while a phospho-mimetic S338D CRAF mutant potentiates Plk1 activation, mitosis, angiogenesis and tumor progression in mice. These findings reveal a previously undefined role for RAF in angiogenesis and tumor progression beyond the RAF-MEK-ERK paradigm, opening new avenues for targeting RAF in oncology.
9:40-10:10 Greg Reyes, M.D,, Ph.D.Senior Vice President, Drug Discovery, CelgeneTitle:
Abstract:
10:10-10:40 Jean Cui, Ph.D.Associate research fellow, PfizerTitle:Invention of Xalkori (Crizotinib): from a Kinase Inhibitor to a Drug
Abstract: Crizotinib, a potent c-Met/ALK dual inhibitor, was fast track approved in August 26, 2011 by FDA for late stage lung cancer patients with EML4-ALK fusion gene based on marked efficacy results from Phase I and II studies. The invention of crizotinib starts from a cocrystal structure of c-Met/PHA-665752 complex. The cocrystal structure ofPHA-665752, bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multi-attribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved withPHA-665752. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group ofPHA-665752via a more direct vector, and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potentin vitroandin vivoc-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties and safety profile.
10:40-11:00 Refreshment Break, Exhibit & Networking
11:00-11:05 Chairperson of session 2
11:05-11:35 Steve Kaldor, Ph.D.Venture Partner at Versant Ventures, acting CEO, QuantiCellTitle:Creating Science and Business Value in San Diego Biotech: Case Studies and Possible Strategies for Future Success
Abstract: In the last 20 plus years, I’ve had the opportunity to participate in the growth of the San Diego biotech industry through my involvement in multiple innovative drug discovery companies, a number of which have produced both marketed drugs and high value liquidity events for investors. In this talk, I’ll highlight several of these companies plus my current work with Quanticel and Versant Ventures. The goal of this talk will be to provide the audience with insights into what has worked, and what is likely to work going forward in creating successful biotech companies which emphasize Research and early phase Development. I’ll also offer some tailored comments on oncology-focused biotechs.
11:35-12:05 Jing Yang, Ph.D.Assistant professor of pharmacology and pediatrics, UCSD

Title: Exploring a New Twist on Tumor Metastasis
Abstract: Tumor cells acquire the ability to degrade basement membrane and extracellular matrix (ECM) in order to invade and metastasize to distant organs. The molecular triggers for matrix degradation in tumor cells are largely unknown. The Twist1 transcription factor plays key roles in tumor metastasis and is known to induce Epithelial-Mesenchymal Transition (EMT).Here we report a novel function of Twist1 in promoting extracellular matrix degradation by inducing the formation of invadopodia.Invadopodia are specialized actin-based membrane protrusions that degrade ECM via clustering of proteases. Twist1 induces PDGFR? expression, which in turn activates Src kinase in various breast tumor cells. Phosphorylation of multiple invadopodia components by Src kinase promotes invadopodia assembly and matrix degradation. We show that Twist1 and PDGFR? are central mediators of invadopodia formation and ECM degradation in response to various EMT-inducing signals, including TGF? and Snail1. Induction of PDGFR? and invadopodia is essential for the ability of Twist1 to promote invadopodia formation, local tumor invasion, and distant metastasis in vivo. Consistent with PDGFR? being a direct transcriptional target of Twist1, expression of

Twist1 and PDGFR? is highly correlated and associated with poor survival in breast cancer patients. Together, our study demonstrates that invadopodia-mediated matrix degradation is a key function of

Twist1 in promoting tumor metastasis. Furthermore, it reveals that matrix degradation and loss of cell adhesion are regulated by different EMT-inducing transcription factors. This explains why multiple factors need to be activated coordinately to promote carcinoma cells to undergo EMT and invade. We also identify PDGFR? as a direct transcriptional target of Twist1 in promoting invadopodia formation and tumor metastasis, therefore suggesting that PDGFRs might be potential targets for anti-metastasis therapies.

12:05-1:00 Lunch
1:00-1:05 Chairperson of session 3 Marie Zhang, Ph.D. MBACo-Founder and COO of MicroStem, Inc.
1:05-1:35 Isan Chen, M.D.Chief Medical Officer, Aragon

Title:Challenges and Opportunities in Oncology Drug Development

Abstract: Drug development is a high-risk industry and the field of oncology clinical development is specially challenging. Present clinical development paradigm is not sustainable in the long term. Close collaboration to remove unnecessary barriers among industry, and between industry and academia is necessary. Understanding the regulatory environment and the disease landscape are critical.An example of the challenges facing drug development in prostate cancer is presented.
1:35-2:05 Tannishtha Reya, Ph.D

Professor, Department of Pharmacology, UCSD

Title:Understanding the Dynamics of Cancer: from Developmental Pathways to in vivo Imaging

Abstract:
2:05-3:05 Panel Discussion:Moderator: Yi Liu, Ph.D.Vice President, Intellikine

Panelists:

David Cheresh, Ph.D.

Professor of Pathology, Associate Director for Translation Research, Moores UCSD Cancer Center

Greg Reyes, M.D., Ph.D.

Senior Vice President, Drug Discovery, Celgene

Isan Chen, M.D.

Chief Medical Officer, Aragon

Jeremy Barton, M.D.

Vice President Precision Medicine, Pfizer

Steve Kaldor, Ph.D.

Venture Partner at Versant Ventures, acting CEO, QuantiCel

Tannishtha Reya, Ph.D

Professor, Department of Pharmacology, UCSD

3:05-3:10 Closing Remarks: Wen Luo Ph.D.,CSO, Denovo Biomarkers