UCSF Molecular Oncology Initiative/ Q&A with Alejandro Sweet-Cordero, MD

By Vicky Agnew | June 14, 2018

As UCSF increasingly leads the way in precision medicine, especially for cancer, the Cancer Center’s Molecular Oncology Initiative (MOI) has become central to those efforts. Using the UCSF500 gene panel assay, the MOI’s focus is on integrating genomic findings from molecular diagnostic tests with the ever-increasing number of therapeutics being developed in translational research and clinical practice to improve patient outcomes. Below, Alejandro Sweet-Cordero, MD, director of the MOI, talks about the unique UCSF 500 assay, how the MOI has grown, and what’s ahead.
 
Q. The Cancer Center launched the MOI in 2015? What is its central purpose? 
The central purpose is to facilitate the use of precision cancer medicine to improve the care of oncology patients, both adult and pediatric.  Precision cancer medicine is the practice of sequencing patient tumors and using that information to inform individualized therapy. The MOI seeks to bring together scientists and clinicians at UCSF to develop new tools and new approaches to facilitate precision cancer medicine for both adults and children.  With children, the MOI has already proven to be extremely useful, particularly for patients with very rare or difficult to treat cancers. 
 
UCSF Cancer News

Alejandro Sweet-Cordero, MD  

"We offer a singular and potentially helpful service to outside physicians through the molecular tumor board and UCSF500 testing...Referring physicians can present their cases at the MOI and get a multidisciplinary perspective with expertise available at only a very few centers nationwide."

Q. What has the MOI accomplished? Has it expanded/grown, either with more projects or contributors?
The main accomplishment of the MOI has been to organize and run the molecular tumor board. The tumor board is a multidisciplinary meeting where clinicians can get help in interpreting sequencing results to define the best therapy for their patients. 
 
Q. What is the UCSF500? Is it unique? Do any other institutions have anything like it?  
Many institutions have precision cancer medicine programs.  Some institutions focus on developing the actual sequencing test.  Others use commercial vendors for the sequencing and focus on what happens after that. At UCSF, we have one of the few fully-integrated programs where we have developed our own assay (the UCSF500) and through the molecular tumor board, help clinicians interpret the results to benefit their patients. The UCSF500 is a unique test because it was designed with both adult and pediatric patients in mind. It studies the tumor itself while also looking at the patients normal DNA. In this way, we are able to identify those patients that have a genetic predisposition to cancer, something that can be very important for future surveillance and to define therapeutic options. 
 
Q. How has the UCSF500 contributed to the rapidly-evolving landscape of cancer treatment?
The UCSF500 test has helped patients in three important ways:  1) clarifying the diagnosis 2) identifying new therapeutic options and 3) identifying patients with heritable cancers. 
 
Q. The Molecular Tumor Board is a central element of the MOI. What is it? How does it work? Is it active?
The molecular tumor board is a multidisciplinary meeting consisting of oncologists, pathologists, bioinformatics scientists, pharmacists, and other experts who meet to discuss individual cases and help provide a recommendation for management of that patient. 
 
Q. There’s a lot of public discussion about sequencing the tumors of as many patients as possible. What does it mean to sequence a tumor? How does that guide treatment?
Sequencing generally means looking at the DNA in a tumor to find how the tumor DNA is different from the normal DNA of the patient.  In a patient without cancer, all cells have the same DNA sequence.  In a tumor, changes in this sequence can help us understand what is causing that cancer and how best to treat it. 
 
Q. Which tumor types are appropriate for profiling?
Usually, we focus sequencing studies on patients who have not responded to standard therapies or patients who have unusual or difficult-to-classify tumors. 
 
Q. Is it realistic or even necessary to sequence as many tumors as possible?
The more tumors we sequence, the more we learn about what causes cancer, but we need to balance this with the expense of doing the test. 
 
Q. Are there more targets than drugs right now?
Drug development is a slow and laborious process that takes many years. These days, sequencing is fast and relatively inexpensive.  So there are many more targets than we have available drugs. 
 
Q. How does the MOI, to include the molecular tumor board, allow us to help referring physicians in ways other regional providers cannot?
Referring physicians can present their cases at the MOI and get a multidisciplinary perspective with expertise available at only a very few centers nationwide.  The UCSF500 is a unique and powerful test that no one else regionally can offer to a patient.  So, we offer a singular and potentially helpful service to outside physicians through the molecular tumor board and UCSF500 testing. 
 
Q. UCSF recently joined the AACR’s Project GENIE. What is GENIE? What are the benefits of participating?
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project genie
Project GENIE is a national consortium of leaders in precision cancer medicine who have agreed to deposit data from their patients in a de-identified registry.  This allows us to see patient data that may have mutations similar to a case we are studying here. This is potentially very useful because we can learn from each other what works and what doesn’t work when interpreting genomic cancer data. 
 
Q. What’s ahead for the MOI and tumor profiling in general? What are members excited about?
We are working very hard to create infrastructure for data sharing so that in the next six months or so any clinician at UCSF will be able to quickly look through the de-identified sequencing data of any patient sequenced here. This can help us better design clinical trials using new therapies. We are also working closely with UCSF experts in extracting medical record information that will allow us to better understand how clinicians use therapeutic recommendations to help their patients. So, if we recommended drug X, did the clinician actually give it to the patient? If so, did it help them, if not, why not?
 

Read more about the Molecular Oncology Initiative.