A multi-disciplinary team of researchers at the Institute for Molecular Medicine Finland, FIMM, and the Helsinki University Central Hospital has developed a novel individualized systems medicine (ISM) strategy which enables selection of potentially effective cancer therapies for individual patients. Furthermore, this strategy helps in understanding and predicting drug resistance and may pave a path for individualized optimization of patient therapies in the clinic for various types of cancers.
Many novel targeted drugs have been introduced to the clinic for cancer therapy, often guided by genomic clues on disease pathogenesis. Clinical treatment of cancer patients is, however, challenged by the fact that genomics is often not informative in selecting therapies to individual patients. Patients also often develop resistance to therapies that were initially effective. Furthermore, tumor heterogeneity and clonal evolution over time within an individual patient make it difficult to apply cancer genomics as a guide to patient therapy.
ISM combines genomics with comprehensive drug sensitivity testing of patient cells to facilitate optimization of safe and efficacious cancer therapies for individual patients. Furthermore, the ISM strategy aids in understanding and predicting how drug resistance evolves and how it may be prevented.
Results achieved by applying this strategy to 28 patient samples have been recently published in the Cancer Discovery journal.
Most of the patients studied had chemoresistant adult acute myeloid leukemia (AML), a disease characterized by poor prognosis. AML is today largely treated by the same chemotherapeutic agents as applied 30-50 years ago. Here, the researchers measured the response of patients’ cells to a panel of 202 cancer drugs covering all approved and many emerging cancer drugs. A list of the most likely effective and ineffective drugs was created for each individual patient and passed on to the treating physician to consider.
Several patients benefited from the therapy selected based on the drug sensitivity testing results. For example, one patient previously unresponsive to three rounds of chemotherapy achieved complete clinical remission with a treatment optimized with the ISM platform.
Leukemia is a cancer of the blood cells.
While the exact cause(s) of leukemia is not known, risk factors have been identified.
Leukemias are grouped by how quickly the disease develops (acute or chronic) as well as by the type of blood cell that is affected (lymphocytes or myelocytes). The four main types of leukemia include acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelocytic leukemia (AML), and chronic myelocytic leukemia (CML).
People with leukemia are at significantly increased risk for developing infections, anemia, and bleeding. Other symptoms and signs include easy bruising, weight loss, night sweats, and unexplained fevers.
The diagnosis of leukemia is supported by findings of the medical history and examination, and examining blood and bone marrow samples under a microscope.
Treatment of leukemia depends on the type of leukemia, certain features of the leukemia cells, the extent of the disease, and prior history of treatment, as well as the age and health of the patient.
Most patients with leukemia are treated with chemotherapy. Some patients also may have radiation therapy and/or bone marrow transplantation.
There is no known way to prevent leukemia.
The prognosis of leukemia depends upon several factors, including the patient’s age, the type of leukemia, and the extent to which the cancer has spread.
Leukemia facts medical author: Melissa Conrad Stöppler, MD
“We integrate three complementary information sources, drug testing results, genomic profiling of cancer cells and clinical information. Repeated sampling of patients plays a major role in understanding and learning from each success and failure”, explains Krister Wennerberg, one of the principal investigators behind this study.
“We are very excited about this ability to provide a truly individualized approach to patient treatment”, says hematologist Kimmo Porkka. “In the future, this may pave the way for testing of all types of human cancers”.
“It is also important to note that we now tested severely ill patients, completely refractory to current therapies”, says Director Olli Kallioniemi from FIMM. “In the future, we hope to impact on therapy of earlier leukemia patients and design effective combinations of treatments”.
Treatment for Leukemia
Leukemia is not a single disease. Instead, the term leukemia refers to a number of related cancers that start in the blood-forming cells of the bone marrow. There are both acute and chronic forms of leukemia, each with many subtypes that vary in their response to treatment. In addition, children with leukemia have special needs that are best met by care in pediatric cancer centers. Such centers have trained medical professionals whose sole purpose is to address the unique concerns of children.
Leukemia treatment plans often are personalized and geared toward each individual patient. In general, there are five major approaches to the treatment of leukemia:
chemotherapy to kill leukemia cells using strong anti-cancer drugs;
interferon therapy to slow the reproduction of leukemia cells and promote the immune system’s anti-leukemia activity;
radiation therapy to kill cancer cells by exposure to high-energy radiation;
stem cell transplantation (SCT) to enable treatment with high doses of chemotherapy and radiation therapy; and
surgery to remove an enlarged spleen or to install a venous access device (large plastic tube) to give medications and withdraw blood samples.
Oncologists administer these treatments in a variety of combinations. Each method has its advantages and drawbacks. It usually is worthwhile to get a second opinion about treatment before entering into a specific program; in some instances, a second opinion may be required by the patient’s insurance company. For example, stem cell transplantation (SCT) is very costly and entails a long stay in the hospital. Some insurance companies still consider this to be an “experimental” procedure and will not pay for SCT-related expenses.
The treatment of leukemia depends on a number of factors. The most important of these are the histopathologic (diseased tissue) type of leukemia, its stage, and certain prognostic features, such as the patient’s age and overall health.
With the ISM strategy, researchers are now able to generate hypotheses to be tested in clinical trials, both for existing drugs, emerging compounds and their combinations. In addition, this approach provides a way to prioritize emerging drugs that are likely to have the best success in clinical trials and ultimately reach routine patient care. Therefore, ISM may pave a path for optimizing pharmaceutical drug development pipelines as well as changing the standard of clinical care so that all patients receive individualized treatment.
Institute for Molecular Medicine Finland (FIMM) is an international research institute in Helsinki focusing on human genomics and personalized medicine. FIMM is hosted by the University of Helsinki and is part of the Nordic EMBL Partnership in Molecular Medicine. FIMM integrates molecular medicine research, technology center and biobanking infrastructures “under one roof” and thereby promotes translational research and adoption of personalized medicine in health care. FIMM technology centre and biobanking infrastructures provide research services for local, national and international customers. In 2012, FIMM had a staff of 185 and an annual budget of 14 million euros, with competitive external funding accounting for 70% of the budget.