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The Treehouse Childhood Cancer Initiative is working to change the story for childhood cancer patients by leveraging genomic data and computational approaches to identify less toxic and more effective treatments. We do this by analyzing a child’s cancer data against both childhood and adult patient cohorts across all types of cancer, comparing individual pediatric tumors against a vast database of 11,000+ tumors. This “pan-cancer” analysis of adult and pediatric tumors may predict situations in which an adult drug might work on a subset of pediatric patients. We support the sharing and distribution of genomic information to researchers everywhere because large genomic datasets can be used as comparison data, offering clinical teams the genomic information needed to better understand what is happening with kids who are suffering from relapsed, refractory and rare cancers.

Synovial sarcoma is a rare and aggressive cancer which occurs most commonly in the arms and legs, near joints and tendons. With support from The Live for Others Foundation, founded by teenager Tim Vorenkamp who tragically passed away from synovial sarcoma in 2016, Treehouse is now able to focus research efforts on accessing synovial sarcoma tumor data from different institutions, including hospitals and research centers, to improve comparative computational analysis we can provide for children currently in treatment with a synovial sarcoma diagnosis. Over the last year, we have more than doubled the number of synovial sarcoma tumor data in our database. We are currently working to assess additional synovial sarcoma data, which will further enhance the value of our research.

Ultimately, the goal of Treehouse is to offer synovial sarcoma cancer patients hope by connecting the dots: when we can point to molecular-level similarities linking a patient’s cancer with cancer tumors that were treated successfully, new treatment possibilities open.

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Nationwide Children’s Hospital and UCSC Treehouse Scientists Embark on Genomic Data Sharing

SANTA CRUZ, CA – October 16, 2018  – Last month, scientists from the UCSC-based Treehouse Childhood Cancer Initiative welcomed Dr. Elaine Mardis and other members of the Nationwide Children’s Hospital’s Institute for Genomic Medicine (IGM) to the UC Santa Cruz campus to bolster an ongoing collaboration focused on pediatric cancer genomics data sharing.

UC Santa Cruz Genomics Institute Scientific Director and Treehouse co-founder Dr. David Haussler said he is excited about the possibilities that could come out of the Treehouse-Nationwide Children’s collaboration. “We believe that genomic data sharing is fundamental to defeating pediatric cancer,” Haussler said. “We are thrilled to be working with Nationwide Children’s Hospital and Dr. Mardis. Her visit to UCSC was inspiring, and we look forward to ongoing research in partnership with Nationwide Children’s world-class cancer care team, which we hope will help their clinicians identify potential treatments,” he concluded.

According to Treehouse co-founder and UC Santa Cruz assistant professor of Molecular, Cell and Developmental Biology Dr. Olena Morozova Vaske, Treehouse analyzes each patient’s tumor RNA sequences in the context of genomic data from thousands of pediatric and adult tumors. This approach may suggest targeted, less toxic and more effective treatments for patients whose cancer has not responded to standard therapies. “Having access to large RNA sequence datasets from multiple tumors is essential to our work. In collaboration with Nationwide Children’s, we are implementing a federated model of data sharing where IGM runs our analysis program at their institution and shares outputs with Treehouse. Nationwide Children’s leadership in genomic pediatric cancer research is vital to our learning, and improves not only our cohort of data but our analysis.”

This federated approach to data analysis allows researchers to match genomic data from individual pediatric cancer patients with other patients in the Treehouse database, making it possible to confirm diagnoses and identify cancer treatments without having to share large raw data that contains identifiable information. Isabel Bjork, Director of Precision Medicine for the UCSC Genomics Institute, continued, “It’s a program that preserves patient privacy while maximizing scientific collaboration.”

According to Dr. Mardis, discovery-based cancer genomics research during the last decade has made significant progress uncovering the genomic underpinnings of pediatric cancers. “These findings have brought us to a point where we can apply them to understand each patient’s cancer in the clinical setting. However, in so doing, we are reminded us there is strength in numbers, especially due to the fact that pediatric cancer is a rare disease.” she opined.  “This is why we are so keen to both utilize and share data with the Treehouse Project: it permits us to readily contextualize each patient in comparison to all other patients in the Treehouse database, and by adding patient data from IGM studies, we can further enable the efforts of other groups who are pursuing precision cancer medicine for pediatric patients.”

During a lecture to about 80 UCSC staff, faculty and students, Dr. Mardis explained that many efforts are underway to address the clinical challenge of treating pediatric patients with relapsed or difficult-to-treat cancers using genomic technologies and advanced analytical approaches. She presented these challenges and identified current approaches to address them, sharing anecdotes about successes and failures, with a hopeful look to the future.

You can learn more about the Treehouse Childhood Cancer Initiative at the UC Santa Cruz Genomics Institute at treehousegenomics.ucsc.edu.

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Featured Photo caption: (Left to right) Ellen Kephart, Kevin Karplus, Andrew Blair, Rob Currie, Vinay Poodari and Mark Akeson went bald in 2017, helping raise more than $12,000 for Treehouse’s Brave the Shave Fundraiser, sponsored by the Genomics Institute

Author: Arjun Rao, Katrina’s cousin

As Treehouse gears up for another #BravetheShave event for St. Baldrick’s, we’d like to highlight some of our outstanding shavees from the previous year. A diverse group of individuals including students, professors, and researchers, came out to support the funding of pediatric cancer research.

Arjun Rao was a graduate student at UCSC when he developed his ProTECT pipeline for use in predicting T-cell epitopes for cancer therapy. His ProTECT pipeline was originally conceived for use on pediatric patient data to help physicians find immunotherapy treatments, which then progressed to being broadly applied to all types of cancer. At a 2016 fundraising event, Arjun shared that when he heard Katrina Learned speak about Aurora’s pediatric cancer at our first fundraiser in 2014, he was inspired to focus on pediatric cancer for his Ph.D..

Aurora’s cousin and Katrina’s nephew, Kian Witten-Hannah, marked his first year as a shavee in 2017 and is excited to shave again this coming year.

Professor Kevin Karplus of the Biomolecular Engineering department negotiated with students and faculty to raise a startling amount of money in return for shaving his head, eyebrows and beard! Along with Professor Karplus, Professor Mark Akeson returned for a second year to shave his head.

Rob Currie and Ellen Kephart are both Treehouse software engineers that also jumped in on the fun last year. Ellen was our only female participant in 2017!

We’re excited for the 2018 #BravetheShave event and we want you to join! If you would like to sign up to be a shavee, donate, or get involved, visit stbaldricks.org/events/UCSC2018.

Arjun Sao, 2017 Brave the Shave event.

Kian Witten-Hannah, 2017 Brave the Shave event.

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Researchers at Treehouse Childhood Cancer Initiative investigate a full range of pediatric cancers. Sarcomas — and particularly, rare sarcomas —  are a focus of our work. Because July is Sarcoma Awareness Month, we’d like to focus this month’s post on this type of cancer. Sarcomas are a type of cancer that specifically targets either the soft tissues (fat, muscle, nerves, fibrous tissues, blood vessels, and deep skin tissues) or bone tissue. Pediatric sarcomas show up in children of all ages. They often appear first in the extremities — for example, as a lump or swelling in a leg. Considered to be one of the rarest forms of malignant sarcoma, synovial sarcoma occurs in the extremities of the arms and legs, in close proximity to the joint capsules and tendon sheaths. With almost half of reported cases of synovial sarcoma occurring in pediatric patients, it’s a priority for Treehouse. Treehouse is dedicated to helping defeat rare and deadly pediatric sarcomas. We analyze large datasets to draw comparisons between genomic data from a child’s tumor and genomic data from similar tumors that clinicians may have treated successfully. Earlier this month, Treehouse was to honored to host Pieter and Petra Vorenkamp from the Live for Others Foundation (L4OF.org), an organization committed to finding a cure for synovial sarcoma. Pieter and Petra’s son, Tim Vorenkamp, passed away after a five-year battle with synovial sarcoma. Before his passing, Tim established the Live For Others Foundation in December of 2015 to help find a cure for synovial sarcoma. Pieter and Petra’s visit to Treehouse included a tour of the Haussler Lab, where Olena (Morozova) Vaske and David Haussler showed them research underway that uses organoids to study the genomics associated with brain size in humans. In a timely gift, Live For Others Foundation also presented Treehouse with a check for $50,000. This money will extend the California Institute for Precision Medicine (CIAPM) supplemental funding for Treehouse’s research. We’d like to thank the Live For Others Foundation for their significant support, and express our hope that genomic data analysis will help patients like Tim get effective treatment in the very near future.

Pieter Vorenkamp from Live For Others presents their generous gift


Pieter and Petra Vorenkamp from Live For Others visiting the Treehouse Team

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Author: Devika G. Bansal

In May 2012, an eight-year-old boy named Kelvin was diagnosed with an unusual cancer called a sarcoma, a tumor not typically found in the brain. His doctors took an aggressive approach: They removed the tumor and gave him six cycles of high-dose chemotherapy. The tumor subsided.

But one year later, the fast-dividing tumor cells had spread from his brain into his lungs. Kelvin lost his appetite and 20 pounds, and he was too tired to go to school. A fresh round of chemotherapy brought no results. The situation was grim. “Most people with relapsed sarcoma of that kind would live not more than three months,” says Rod Rassekh, Kelvin’s oncologist at the British Columbia Children’s Hospital in Vancouver.

At this point, deciding that more chemotherapy would be futile, Rassekh decided to try a new approach called “precision medicine”, in which patients get personalized treatments tailored to their genetic make-up and history. He contacted Olena Morozova, a bioinformatician at the the Treehouse Childhood Cancer Initiative, a project at UC Santa Cruz, a group that uses genomic data to identify therapy. Treehouse is one of five nationwide precision medicine consortiums aimed at pediatric cancer, and it’s the only one on the U.S. West Coast. Rassekh hoped that Morozova could supplement his own analysis to help find a treatment that would work for Kelvin’s unique condition.

[Read More]

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In observance of Cancer Immunotherapy Month in June, we have invited guest contributor Shawn Tallet, Outreach Coordinator for the Mesothelioma & Asbestos Awareness (MAA) Center to offer a brief look at immunotherapy, its history and promise as a treatment. We are particularly excited about the possibility of immunotherapy for use in pediatric cancer, and happy to share the following update.

Tremendous strides have been made in the field of oncological research and treatment, but perhaps the most sustainable and discernable advancements fall within the realm of immunotherapy. Broadly speaking, immunotherapy is the use of the body’s own immune system to combat and eradicate cancerous cells. Today, several different types of immunotherapy are used in treating the disease, including cancer vaccines and antigen therapy. The success rate has been climbing substantially, and certain treatment regimens have been effective in combating pediatric cancer and other rare diseases, as well as providing patients a less toxic therapy option.

Early Beginnings

Although immunotherapy can be traced back to the late 19th century, its practical application and understanding wasn’t fully integrated into cancer care until the 1990s. Dr. William B. Coley, MD, is generally considered the first practitioner who championed immunotherapy in the late 1800s. Dr. Coley’s theory that live and inactivated antigens injected directly into tumors would elicit an immune response was accurate, and some patients with sarcomas, lymphoma, and testicular carcinoma went into spontaneous remission. This strategy was continually extrapolated upon throughout the 20th century, resulting in a major breakthrough in 1976. Researchers were able to pinpoint T-cell growth factors and understand their interaction with cancer cells. Antibody therapy regimens and cancer vaccines were eventually discovered and offered in clinical trials, with the first Food and Drug Administration (FDA) approval occurring in 2010. These vaccines were shown to extend overall survival rates in clinical trials, and many childhood cancers have been included in these experimental treatments, including non-Hodgkin lymphoma, neuroblastoma, and several types of leukemia.

Modern Therapy

There are many variables associated with the decision to start immunotherapy, and they should be thoroughly discussed with one’s oncologist. Since many types of immunotherapy are still in experimental phases, they are not always approved by the FDA. However, because immunotherapy uses the body’s own defense system to fight disease, side-effects are generally more mild than regimens like chemotherapy and radiation therapy which use toxins to destroy cancer cells. Certain pediatric cancers have seen great success in treatment with monoclonal antibody therapies, most notably relapsed B-cell acute lymphoblastic leukemia (ALL), which is treated with FDA-approved KYMRIAH, a therapy specially designed for patients under 25 years of age. Furthermore, vaccination clinical trials targeting neuroblastoma, as well as sarcomas in infants and young children, can be successful. Additionally, some rare diseases have shown positive responses to immunotherapy treatments. Patients with mesothelioma, a rare disease caused by asbestos exposure, have had success with immunotherapy treatments used for non-small cell lung cancer. Under the right circumstances, including overall patient health and stage of cancer, these treatment procedures have resulted in the reduction of cancerous growth and even near complete remission.

What Does the Future Hold?

With the rate of medical research and advancement occurring throughout the world, the sense of optimism in cancer treatment is at an all-time high. Immunotherapy is perhaps the most cutting-edge mode of treatment in development and moves away from types of treatments with known toxicities to patients, like chemo and radiation therapy. In the past two years incredible progress has been made in the field, with milestones including gene editing to prompt immune cells to fight cancer (University College London, April 2016) and FDA approvals of CAR-T therapies (University of Pennsylvania, August 2017).

This extensive study of the immune system’s potential moves the world one step closer to finding the ultimate cure to end cancer.

For more information on immunotherapy and the MAA Center, visit www.maacenter.org/treatment/emerging-treatments

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Case Report in JCO, Precision Oncology

Clinical detection of sequence and structural variants in known cancer genes points to viable treatment options for a minority of children with cancer.1 To increase the number of children who benefit from genomic profiling, gene expression information must be considered alongside mutations.2,3 Although high expression has been used to nominate drug targets for pediatric cancers,4,5 its utility has not been evaluated in a systematic way.6 We describe a child with a rare sarcoma that was profiled with whole-genome and RNA sequencing (RNA-Seq) techniques. Although the tumor did not harbor DNA mutations targetable by available therapies, incorporation of gene expression information derived from RNA-Seq analysis led to a therapy that produced a significant clinical response. We use this case to describe a framework for inclusion of gene expression into the clinical genomic evaluation of pediatric tumors.

CASE SUMMARY

Patient 1 was diagnosed at 8 years of age with a left tentorial-based CNS sarcoma after a 2-week history of nausea, lethargy, and diplopia. Clinical workup confirmed that the tumor was primary to the brain (Figs 1A and 1B). Histology revealed a mitotically active, epithelioid-to-spindled cell tumor in patternless sheets, interrupted by thick fibrous bands and foci of necrosis (Figs 1C to 1D). Immunohistochemistry revealed diffuse positivity for vimentin, desmin, neuron-specific enolase, epithelial membrane antigen, and CD99 (Figs 1E to 1H). Focal immunohistochemical positivity was observed for pan-cytokeratin (AE1/AE3) and synaptophysin. The tumor was negative for glial fibrillary acidic protein (GFAP), Wilms tumor 1 (WT1), myo-D1, myogenin, smooth muscle actin, nonphosphorylated and phosphorylated neurofilament protein, CD34, CD31, HMB-45, S-100, leukocyte common antigen, and BAF47/INI-1 (retained nuclear positivity). The Ki67 proliferative index was 9%. A diagnosis of desmoplastic small round cell tumor (DSRCT) was favored initially.7 Because EWSR1 breakapart fluorescence in situ hybridization confirmed an EWSR rearrangement but concomitant WT1 breakapart fluorescence in situ hybridization was negative, the molecular criterion for DSRCT was not met, and a final diagnosis of poorly differentiated sarcoma, not otherwise specified, was rendered. The patient received six cycles of induction chemotherapy—ifosfamide, carboplatin, and etoposide—followed by autologous stem-cell transplantation with a high-dose preparative regimen of carboplatin, thiotepa, and etoposide as well as 54 Gy of focal radiation to the location of the original tumor. After a 2-year remission, the tumor recurred with numerous pulmonary lesions in all lobes. The histologic characteristics of the metastasis were identical to the primary tumor. The patient enrolled in the Personalized OncoGenomics (POG)3 study, which offers whole-genome sequencing (WGS) and transcriptome sequencing and analysis to identify drivers and potential therapeutic options of relapsed solid tumors for children and adults in British Columbia.

Read more.

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Treehouse Childhood Cancer Initiative by Treehouse Genomics - 8M ago

On a chilly February morning in UCSC’s Quarry Plaza, we came together to raise awareness and some funds for the Treehouse Childhood Cancer Initiative, the pediatric cancer research arm of the UC Santa Cruz Genomics Institute. Staff members Ann Durbin and Katrina Learned were aided by two student members of the Treehouse team, 2nd year Preet Kaur and 3rd year, Stephanie Dittrich, who joined just in time to help organize this event. Steph and Preet met representatives from exciting organizations also involved in Giving Day 2018, including Engineers Without Borders and Sigma Mu Delta. Our collaborators from UCSC’s WiSE (Pauline Blaimont and Tori Klein) worked with us to carry out strawberry DNA extractions — always a hit!  

At the end of the 24-hour period, we’d given out dozens of our new brochures, shared delicious cookies donated by the good folks at Pacific Cookie Company, made new friends from all over campus, and raised over $3000 in donations from 23 supporters. All the moneys raised support our mission: to promote sharing of the world’s genomic data, and harness that data to defeat every child’s cancer.

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