Bay Area LifeTech Hosts Young Innovators in Oncology

By: Karen Ring, PhD

Bay Area LifeTech (BALT) hosted an event titled “Young Innovators in Oncology” at the Netherlands Consulate General in San Francisco on December 5, 2013. The talk featured three speakers, two academics, Francesca Gazzaniga and Marvin Tannenbaum from UCSF, and an entrepreneur, Shawn Carbonell from OncoSynergy. The event brought in new faces from all over the bay area including a high school student who was interested in Cancer research. Luke Lightning, PhD, founder of BALT, along with support from Robert Thijssen and Natasha Chatlein of the Netherlands Office of Science and Technology (NOST) succeeded in throwing another captivating and informative event. Below are summaries of the talks by the three speakers.  

Francesca Gazzaniga is a graduate student in Dr. Elizabeth Blackburn’s lab at UCSF. Dr. Blackburn received the Nobel Prize in Physiology or Medicine in 2009 for her discovery of the telomerase enzyme and how it maintains telomere length. Telomeres are sequences of DNA at the ends of chromosomes that act as caps that prevent chromosome shortening and loss of important genetic information during cell division. Francesca’s graduate research focuses on the role of telomerase in breast cancer. Breast cancer is the number one cause of cancer-related death in women and accounts for almost 30% of all diagnosed cancers in women. Breast cancer is a heterogeneous disease, which is why having a library of tissue samples or cancer cell lines is extremely valuable for studying this disease. Francesca has access to 50 human breast cancer cell lines and made it her goal to study telomerase activity and telomere length in each of these lines. Interestingly, she and Dr. Imke Listerman, a postdoc in the Blackburn lab, found that both telomerase activity and telomere length varied in all 50 lines and that telomerase activity was elevated in basal breast tumors, which is the most metatstatic form of breast cancer. She also identified specific genes and cell signaling pathways that correlated with telomerase activity and telomere length in these cancer cell lines. The telomerase gene, hTERT, correlated with telomerase activity, which was to be expected. Interestingly, the apoptotic pathway, a form of cell death, also correlated with telomerase activity. Francesca suggested that new therapies targeting breast cancer in women should use a two-pronged approach that targets both telomerase activity as well as cell death.

Marvin Tannenbaum, PhD, is a postdoctoral scholar in Dr. Ron Vale’s lab at UCSF. Dr. Vale received the Lasker Award in 2012 and is an expert in studying molecular motors, which are proteins that carry cargo to different parts of the cell along tracks called microtubules. Marvin’s postdoctoral work focuses on the role of molecular motors in cell division and cancer. Cell division (or mitosis) is a mechanical process, which involves the duplication and separation of chromosomes coordinated with the division of the cell. A bipolar mitotic spindle composed of microtubules and molecular motors mediates chromosome segregation. A specific molecular motor, Eg5, promotes bipolar spindle assembly and is essential for proper chromosome segregation. Inhibition of Eg5 function results in the formation of a monopolar spindle structure and prevents chromosome segregation and cell division. Cancer cells are notorious for uncontrolled cell division and consequently, inhibition of Eg5 has been pursued as a target to halt cancer cell growth. Eg5 inhibitors are already in clinical trials and results so far show low toxicity but also low efficacy with tumors acquiring resistance early on in treatment. Furthermore, cancer cells can grow and divide without Eg5 function. Marvin hypothesized that other molecular motors must compensate for Eg5 function. Using an RNAi knockdown screen, he was able to identify Kinesin12 (K12) as the molecular motor that can act with Eg5 to promote bipolar spindle assembly. When he inhibited Eg5 function and overexpressed K12, he saw that cells could still form bipolar spindles and divide, proving that K12 can take over Eg5 function. Furthermore, when he took Eg5 resistant cancer cells and treated them with RNAi against K12, he saw 100% formation of monopolar spindles and no cell division. Thus Marvin proposed that he has found an alternative target for treating cancer cells that are resistant to Eg5 inhibitors.

Shawn Carbonell, MD, PhD, is the founder and CEO of OncoSynergy, a biotechnology startup located in Mission Bay, San Francisco. A former brain surgeon trainee turned entrepreneur, Shawn’s goal is to bring “Targeted Synergy” to cancer therapeutics. His company has initially focused on pursing novel therapies for glioblastoma (GB), the most malignant type of brain cancer that has a median survival rate of 12 months. Avastin, a monoclonal antibody developed by Roche, is an inhibitor of angiogenesis (blood vessel formation) and is approved for recurrent GB. Unfortunately, approximately 40% of GB patients are non-responders to Avastin and patients that do respond typically see a more aggressive recurrence of their cancer after several months. Faced with these daunting facts, Shawn proposed an idea that an effective cancer treatment could come in the form of a single drug that attacks a spectrum of cancer promoting mechanisms, i.e., Targeted Synergy. He focused on integrins, which are transmembrane receptor proteins that mediate cellular adhesion and are a critical path for interactions within the tumor microenvironment that drive tumor growth and progression. By using a monoclonal antibody called OS2966, which selectively modulates β1 integrins, Shawn and colleagues were able to inhibit GB cell migration, adhesion, and angiogenesis in vitro. Additionally, they observed complete growth inhibition, a reduction in growth factor receptor expression, and a pro-apoptotic effect in human xenograft models of Avastin-resistant GB. OS2966 is a drug platform that also prevents spontaneous lung metastasis in a triple negative breast cancer model. Shawn believes that OS2966 has blockbuster potential because of its multiple mechanisms of action and dramatic activity in several aggressive cancer models. OncoSynergy plans to initiate Phase I clinical trials in GB in 2016. Additionally, they are developing two other drug platforms called OS47720 and OS342. The latter is being advanced to treat dermal neurofibromas in Neurofibromatosis Type 1. 

As the official blogger for BALT, I’d like to wish everyone the happiest of holidays and thank those of you who have supported and attended BALT events in 2013. I’d also like to give a special shout out to BALT sponsors Cell Signaling Technology, Medline, and NOST. BALT is planning to welcome 2014 with a brand new website and will also be looking for member feedback on fresh ideas for BALT events. Lastly, the next Meetup scheduled is the State of the Life Sciences Industry with Steve Burrill on Thursday, January 16^th 2014 at UCSF, Mission Bay. 

Karen Ring is a Postdoctoral Scholar at the Buck Institute for Research on Aging. To contact Karen, email her at Ring.Karen@gmail.com.