Purdue Cancer Center seminar

My thanks to hosts Drs. Shihuan Kuang and Timothy Ratliff for the opportunity to present our work at the Purdue University Center for Cancer Research seminar series on February 26.  Purdue has exciting programs in muscle & non-muscle stem cell biology & physiology and tissue engineering, and cancer biology.  It was a pleasure to meet with these accomplished scientists and build new collaborations.  

NCI Targeting Rhabdomyosarcoma Workshop

reposted from http://ncifrederick.cancer.gov/events/Rhabdomyosarcoma/ 

NCI Shady Grove
8717 Grovemont Circle
Gaithersburg, MD 20877

Host Institute
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health

Background
Rhabdomyosarcoma (RMS) is the third most common extracranial solid tumor of childhood. Approximately 350 new cases are diagnosed in the United States each year accounting for 3 percent of childhood cancers. RMS is derived from primitive myoblasts and morphologically resembles early stages of prenatal skeletal muscle differentiation. However, a large percentage of RMS tumors occur in locations normally lacking skeletal muscle, with the head and neck, genitourinary tract and retroperitoneum being frequent sites of tumor localization. Development of RMS has been associated with genetic tumor predisposition syndromes including Li-Fraumeni syndrome, neurofibromatosis and Costello syndrome. Childhood RMS is subdivided into two major subtypes, embryonal and alveolar, which have distinct histological features and genetic alterations. Adult RMS is largely a third histological subtype, namely pleomorphic RMS. The alveolar RMS subtype carries a poorer prognosis and is strongly myogenin positive by immunohistochemistry. The embryonal RMS subtype carries a better prognosis and is strongly MYOD1 positive by immunohistochemistry. Treatment for RMS is typically multidisciplinary including surgical resection, chemotherapy and radiation therapy. Relapse-free survival rates with this aggressive treatment regimen approach 70-80% for patients with localized disease. However, the 5-year survival rate for patients with metastatic disease at diagnosis continues to be less than 30%. Improvement in these survival rates is dependent upon identification of RMS-specific molecularly targeted agents.

Recent next-generation sequencing efforts have highlighted several driver mutations in RMS. The drivers for ARMS include the PAX3-FOXO1 and PAX7-FOXO1chimeric transcription factors. In contrast, the drivers for ERMS include mutations in the FGFR4/RAS signaling pathway, loss of heterozygosity at 11p15 (leading to IGF2 overexpression) and chromosome 8 gains. The prognostic significance of these mutations is currently unknown. Of these drivers, only IGF1R has been targeted in clinical trials in RMS, through the use of therapeutic monoclonal antibodies. These agents, including cixutumumab, show limited single agent activity and efficacy is limited by tumor resistance to the targeted agent. Small molecule inhibitors of the RAS-MAP kinase pathway, receptor tyrosine kinases, and reactive oxygen species have been validated and tested in other cancer types. In addition, targeted agents directed against other chimeric transcription factors, such as EWS-FLI1, have been identified. Validation of these targeted agents in RMS is complicated by the lack of a universal pre-clinical animal model of ERMS or ARMS.

The purpose of this meeting is to bring together the leaders in rhabdomyosarcoma basic, genomic, translational and clinical research to share ideas, data, resources and plan for collaborative and synergistic approaches to decipher rhabdomyosarcoma biology and develop novel therapies.

Planning committee
Javed Khan, Fred Barr, Doug Hawkins, Stephen Skapek, Janet Shipley, David Langenau, Charles Keller, Mari Yohe

Funding Sources
Office of Rare Disease (ORDR; http://rarediseases.info.nih.gov/)
Center for Cancer Research (CCR; https://ccr.cancer.gov/)

Hope in the Huffington Post

The Children's Cancer Therapy Development Institute was profiled in the Huffington Post today! 

After President Obama revealed an ambitious plan to support personalized medicine in his 2015 State of the Union address, all eyes turned towards the hope this promise might deliver to families dealing with childhood cancer.

Our General Counsel and resident superdad, Jonathan Agin, profiled how cc-TDI will be part of this promise in his heartfelt, informative column. Read the full piece at HuffPost Impact.

Welcoming Matthew (to cc-TDI)

Matthew Svalina joins cc-TDI from Dr. Keller's academic laboratory as a founding member of our scientific team, with an eye on advancing the most promising childhood cancer therapeutics towards clinical trials. Matthew is motivated by the 1 in 5 children diagnosed with cancer for whom survival is still a challenge.

Matthew earned a Bachelor of Science degree in Biological Sciences with a minor in Chemistry from the University of Illinois in 2007. Following completion of his undergraduate degree, Matthew earned a paramedic license through Malcolm X College in Chicago, where he completed his field internship with the Chicago Fire Department on ambulances serving the south side of Chicago. As a member of the Keller lab, Matthew has already co-authored two scientific papers on childhood cancer, with additional studies nearing submission. Under Dr. Keller's mentorship, Matthew leads basic science and preclinical projects in rhabdomyosarcoma and medulloblastoma. Matthew’s career goal is to be a physician-scientist with training and independent research in neuroscience and neuro-oncology.

  

Postdoctoral Fellowship Available

We are now taking applications for a postdoctoral fellowship studying the tumor microenvironment in the childhood cancer of muscle, rhabdomyosarcoma.  This mentored position will explore at depth the cell-cell communication and signaling pathways responsible for tumor initation and progression. A strong publication record and sense of exploration are requisite.  Candidates with PhD degrees in the biological sciences as well as engineering are invited to apply.  For more information, contact Charles Keller, MD at charles@cc-tdi.org.  

  

Nobel medal sold... then given back

To read the improbably story of an altruistic gift to science, followed by another gracious gift, see the story by Daniel Dunaief here.   
  
[ image source is the original news story website ]

Be a Dog's Best Friend

Can finding new treatments for dogs with soft tissue sarcomas also help develop new drugs for children and adults with soft tissue sarcomas?  This possibility is raised by today's publication by collaborator Milan Milovance entitled, Comparative Pathology of Canine Soft Tissue Sarcomas: Possible Models of Human Non-rhabdomyosarcoma Soft Tissue Sarcoma.  Co-authors of this study include Charles, as well as long time collaborator adult sarcoma pathologist, Atiya Mansoor.  [ pictured: undifferentiated sarcoma (also called UPS, or MFH) in dog and human ]