Systems medicine paves the way for improved treatment for AML patients

A model for other cancer treatments in the future?

A multidisciplinary team of researchers at the Institute for Molecular Medicine Finland (FIMM), and the Helsinki University Central Hospital has developed a novel individualised systems medicine 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 individualised optimisation 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, tumour heterogeneity and clonal evolution over time within an individual patient make it difficult to apply cancer genomics as a guide to patient therapy.

Individualised systems medicine combines genomics with comprehensive drug sensitivity testing of patient cells to facilitate optimisation of safe and efficacious cancer therapies for individual patients. Furthermore, the individualised systems medicine strategy aids in understanding and predicting how drug resistance evolves and how it may be prevented.

In this study, the investigators based individualised systems medicine on molecular profiling and ex vivo drug sensitivity and resistance testing of patients' cancer cells to 187 anticancer drugs, clinical implementation of therapies predicted to be effective, and studying consecutive samples from the treated patients to understand the basis of resistance. The results achieved by applying this strategy to 28 patient samples have been recently published in the Cancer Discovery journal.

Effective/Ineffective Drugs

This is a diagram highlighting the drugs most and least likely to be effective for treatment of a particular patient.

Credit: Tea Pemovska/FIMM

Most of the patients studied had chemoresistant adult acute myeloid leukaemia (AML), a disease characterised 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 optimised with the individualised systems medicine platform.

"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.

According to haematologist Dr Kimmo Porkka, the study team is very excited about ability to provide a truly individualised approach to patient treatment. "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. With the individualised systems medicine 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 prioritise emerging drugs that are likely to have the best success in clinical trials and ultimately reach routine patient care.

Therefore, individualised systems medicine may pave a path for optimising pharmaceutical drug development pipelines as well as changing the standard of clinical care so that all patients receive individualised treatment.

It is worthy to mention that an annual budget of FIMM is 14 million EUR, with competitive external funding accounting for 70% of the budget.

Reference

Pemovska T, Kontro M, Yadav B, et al. Individualized Systems Medicine (ISM) strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov, 2013; 3(12):1416-29. doi: 10.1158/2159-8290.CD-13-0350. Epub 2013 Sep 20.

Systems medicine paves the way for improved treatment for AML patients
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