University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

UCSF Investigators Reflect on Dream Team Collaborations as Stand Up to Cancer Telethon Approaches

By Karen Gehrman | cancer.ucsf.edu | September 6, 2016

UCSF Investigators Reflect on Dream Team Collaborations as Stand Up to Cancer Telethon Approaches

On September 9th, millions of people across the United States and Canada are expected to tune into the fifth biennial Stand Up to Cancer broadcast raising money for cancer research. Since 2008, SU2C has raised more than $370 million and dedicates 100% of funds raised to support collaborative research via its multi-institutional, multidisciplinary Dream Teams.

UCSF involvement and updates from the field

Researchers with UCSF’s Helen Diller Family Comprehensive Cancer Center have been involved in four Dream Teams and awarded a grant for innovative research.

Alan Ashworth, PhD, FRS is known for his work on BRCA2 and participated on the original Breast Cancer Dream Team project.

"The team research model supported and promoted by SU2C and its scientific partner, the American Association for Cancer Research, is critical to making progress against this complex disease,” said Alan Ashworth, PhD, FRS, president of UCSF Helen Diller Family Comprehensive Cancer Center. “It’s the model we follow at UCSF, and it yields discoveries that might not be made otherwise.”


PANCREAS:  SU2C-Lustgarten Foundation Dream Team: Transforming Pancreatic Cancer to a Treatable Disease
Grant Term: July 2014 – June 2017 Total Funding: $8 million 

UCSF principal: Margaret Tempero, MD, director of the UCSF Pancreas Center and former deputy director of the HDFCCC.  UCSF patient advocate: Stuart Rickerson.  

The Dream Team consists of a multidisciplinary group of experts that includes laboratory and clinical researchers, young investigators and senior scientists who have never worked together, and patient advocates. 

"Our SU2C Convergence Dream Team is focused on developing novel immunotherapies for patients with pancreatic adenocarcinomas, the most recalcitrant of all solid tumors, said Tempero.   "Already we are demonstrating that by using vaccines we can recruit effector T cells to the tumor microenvironment.

"With the addition of checkpoint inhibitors and other novel agents, we expect to see increasing clinical benefit. We know we have a hard road ahead, but the rich collaboration within our group really accelerates our progress!"


LUNG:  SU2C-American Cancer Society Dream Team: Targeting KRAS Mutant Lung Cancers
Grant Term: August 2015 – July 2018 Total Funding: $20 million

UCSF Principal:  Frank McCormick, PhD, FRS, professor emeritus and former director, UCSF Helen Diller Family Comprehensive Cancer Center.   McCormick, a pioneer in molecular biology, was tagged to participate in a Dream Team when a $20 million effort began to combat lung cancer in 2015.  

The Lung Cancer Dream Team devised a three-pronged approach to focus on KRAS mutant lung cancer, aiming to define the most effective therapies to target KRAS and critical related biological pathways, to target the immune system for the treatment of KRAS mutant lung cancers, and to integrate targeted therapies with immunotherapies for these lung cancers.


PROSTATESU2C-Prostate Cancer Foundation Dream Team: Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer 
Grant Term: January 2013 – December 2015 with one year extension Total Funding: $10 million

UCSF Lead:  Eric J. Small, MD, chief of Hematology/Oncology and deputy director of the UCSF Helen Diller Family Comprehensive Cancer Center.

“I am incredibly excited about this project. It has the potential to completely transform the way we take care of our patients with advanced prostate cancer," said Small who leads the Prostate Cancer Program and is the principal investigator of the project.

“Despite a number of new drugs that have been approved for this disease, some of which we helped develop at UCSF, many of our patients still develop resistance to these agents and die from progressive disease. This work will help identify the causes of resistance in an individual patient, and help us tailor therapy for that patient.’’


BREAST:  SU2C Breast cancer Dream Team: An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their Resistance Phenotypes 
Grant Term: October 2009 – September 2013 Total Funding: $17.5 million 

UCSF Principal: Zena Werb, PhD, professor and vice-chair, department of anatomy, Helen Diller Comprehensive Cancer Center.  UCSF Investigators: Jayanta Debnath, MD, Hope S. Rugo, MD, Laura J. van’t Veer, PhD.

“SU2C allowed us to pursue novel areas of cancer metastasis at stages of development that would not have been fundable by NIH.  These projects resulted in significant accomplishments of importance to the field," noted Werb.

“The goal of this project was to test the efficacy of individualized treatment of drug-resistant metastatic breast cancers using therapies selected based on the “omic” features of the metastatic tumors. 

"To develop models to study drug resistant metastatic breast cancers, my team pursued two major goals. The first was to reveal novel genes and mechanisms involved in resistance mechanism.  We discovered genes (Zeppo1/ZNF703 and Zeppo2 /ZNF503 and ZNF217) that promote chemo resistance and factors in the tumor microenvironment that regulate chemo resistance. 

"In a second project, we developed patient-derived xenograft models in which human breast cancer fragments were allowed to grow in immunodeficient mice. The tumors that arose were very similar to the original tumors in the patients including metastasis. Subsequently, we developed technology to permit isolation of rare disseminated cells in a variety of distal organs. Using state – of-the-art single cell analysis to characterize these cells, we also provided insight into selectively inhibiting metastasis."

For more details see the full Breast Cancer Dream Team Progress Report.


2016 Innovative Research Grants (IRGs) Awardee

In April 2016, UCSF’s Martin Kampmann, PhD, was selected to receive one of SU2C's latest Innovative Research Grants (IRGs) which support cutting-edge cancer research by early-career scientists who might not receive funding through traditional channels. The projects are known to be high risk but with strong potential to impact patient care.

The grant funds a three-year project in which Kampmann aims to uncover new therapeutic targets in cancer cells.  

“Our project is Weak Links in Cancer Proteostasis Networks as New Therapeutic Targets. We want to target the so-called proteostasis network in cancer cells: the pathways that maintain the integrity of proteins in the cell. The proteostasis network in cancer cells is commonly challenged by dysregulated protein synthesis, overexpression of oncogenes, and protein imbalances caused by aneuploidy (an abnormal number of chromosomes in a cell), making it an attractive but underexplored therapeutic target," said Kampmann who is an Assistant Professor in the UCSF Department of Biochemistry and Biophysics and the Institute for Neurodegenerative Diseases.

“We will leverage CRISPR-based technologies that we co-developed in order to identify specific vulnerabilities. We are teaming up with Jason Gestwicki’s lab at UCSF to develop drugs targeting these vulnerabilities. The SU2C Innovative Research Grant enables us to pursue this high-risk, high-reward research project.”

HDFCCC Alumni

Former UCSF cancer researchers Joe Gray, PhD, and Phillip Febbo, MD, also held key positions on SU2C Dream Teams. Gray co-led the Breast Cancer Dream Team; and Febbo is credited as the architect of the Prostate Cancer Dream Team currently led by Eric Small, MD. 

 

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