Children’s is at the forefront of a new and expanding approach – called
precision medicine or personalized medicine – to treating cancer and blood disorders in
children and young adults.
develops when damage to the DNA code in cells causes them to grow and divide
uncontrollably, eventually forming malignant tumors. Scientists have discovered
that each patient’s cancer is driven by a unique combination of DNA changes,
collectively termed its tumor “profile.”
goal of precision cancer medicine is to individualize treatments by tailoring
them to the genetic characteristics of the patient’s cancer – for example,
selecting drugs matched to the tumor profile. In some cancer types, precision
cancer medicine has decreased the side effects of treatment and/or increased
the effectiveness of treatment. For other cancer types, including many
childhood cancers, it is still not known whether the precision cancer medicine
approach will decrease side effects or increase effectiveness.
Dana-Farber Cancer Institute and Brigham and Women’s Hospital offer one of the country’s most comprehensive precision cancer medicine initiatives, called Profile. Any patient coming to Dana-Farber/Boston Children’s (or for adults to Dana-Farber/Brigham and Women’s) for treatment, consultation, or a second opinion can join the Profile research study. Patients simply provide consent for use of tissue samples for research. No additional biopsies or blood draws are required beyond those already taken for diagnosis or treatment.
All hematological (blood) cancers, solid tumors and brain tumors are studied in the Profile research study. Ultimately, this important research project will result in a database of genetic changes in all types of cancer. The findings of Profile research are advancing scientists’ understanding of the genetic causes of cancer, and how knowing that information may ultimately lead to improved treatment.
Sequencing of the samples, which is done at the Center for Advanced Molecular Diagnostics at Brigham and Women’s Hospital, involves detailed analysis of 300 genes in tumor cells that have been implicated in, or suspected of, causing cancer. This testing can detect mutations – “typos” in the letters of the DNA code – as well as segments of genetic code that are missing or duplicated, and broken or reshuffled chromosomes.
This testing is being performed primarily to increase scientific knowledge. However, if an individual’s test reveals information that could be of clinical benefit, those results will be returned to the patient’s doctor – as long as the patient/family indicated an interest in the results when signing up for the study. Some genetic changes, or mutations, indicate that a certain drug will be particularly effective, while other DNA alterations might indicate that the tumor is resistant to specific treatments.
In certain cases the culprit mutations in a patient’s tumor can serve as “targets” for new designer cancer drugs. Such targeted drugs – unlike conventional chemotherapy – attack specific molecules and processes in cancer cells to shut down their growth, while sparing normal cells and tissues that don’t have these targets.
Completed Study: iCat – Individualized Cancer Therapy
In addition, at Dana-Farber/Boston Children's, patients with pediatric solid tumors that are high risk, recurrent or refractory to conventional therapy were offered the opportunity to participate in the iCat (Individualized CAncer Therapy) protocol, a study conducted at four pediatric cancer hospitals and led by Dana-Farber/Boston Children's. The goal of the study was to determine whether doctors could use genetic testing to identify genetic abnormalities in a patient's tumor and make a specific treatment recommendation based on the results.
iCat investigators screened each patient's tumor against a panel of known cancer-associated genetic alterations. If a matched drug was available through a clinical trial or in an appropriate, FDA-approved formulation, the iCat team made a treatment recommendation to the patient's oncologist.
One hundred patients in total participated in the study. As reported in JAMA Oncology in January 2016, based on their tumor genetic analyses, the iCat investigators made treatment recommendations for 31 patients. In an additional 12 patients, the investigators identified genetic alterations suggesting a different diagnosis and/or revealing that the patient might harbor a cancer predisposition syndrome.
Open Clinical Trial: GAIN – Genomic Assessment Informs Novel Therapy
A follow-up study – the Genomic Assessment Informs Novel therapy (GAIN) consortium study – is open and recruiting patients from 12 centers across the United States, led by Dana-Farber/Boston Children's. In this follow-up protocol, Dana-Farber/Boston Children’s researchers are studying whether a more extensive form of genetic testing called “whole-exome” sequencing may help reveal opportunities to improve treatment. Such testing scans all of the DNA that codes for proteins in a cancer cell, and potentially may detect DNA changes that haven’t previously been linked to cancer.
precision medicine study will determine whether it is possible to use profiling
results to determine a matched targeted therapy for children and young adults with
high-risk leukemia (including relapsed acute lymphoblastic leukemia and acute myelogenous leukemia). It will investigate the range of mutations found in children
with high-risk leukemia, and describe the clinical outcomes of patients who
receive a matched targeted therapy.
study is evaluating the use of specialized testing called leukemia profiling.
Once the profiling is performed, the results are evaluated by an expert panel
of physicians, scientists and pharmacists. This may result in a recommendation
for a specific precision medicine cancer therapy or a clinical trial called
Matched Targeted Therapy (MTT). The results of the leukemia profiling and, if
applicable, the MTT recommendation will be communicated to the participant's
Building on findings from Profile and iCAT, Dana-Farber/Boston Children’s offers a range of clinical trials based on gene alterations. To learn more about our clinical trials, search our clinical trials or email us at firstname.lastname@example.org.
Katherine Janeway, MD, describes how precision medicine is transforming cancer treatment.
A genetic test can explain why a child or young adult developed cancer and can help predict whether he is at risk for other conditions.