Study developed new approaches to the complexity of cancer cells: "Timetable" could help combat resistance targeted drug therapies

Current article ratings:
Patients / public:healthcare Prof:
New drugs that specifically showed the mutant genes responsible for cancer growth objectives for success in the lives of patients, with far fewer side effects than conventional cancer therapies to extend. Unfortunately, many patients are resistant to these drugs with secondary mutations.

An interdisciplinary team of researchers at the UCLA has now developed a "road map" of the complex signaling processes in cancer, which could lead to new methods for the diagnosis and management of drug resistance.

Cancer is gone interconnected events wrong a complex mix of multiple mutations. And while scientists much about these individual events have learned they have long tried a better understanding of how the events together as a system function to cancer cause.

Proteins act as the main components of the physiological metabolic and signaling pathways of cells. With Proteomics - large-scale study of protein interactions and activities - developed the UCLA team a concept for the complexity of the events, which is a cause for cancer screen.

In a study published in the journal Science Signaling March 29, the team demonstrates their network-scale proteomic experiments and mathematical analysis, "System Wide" view on how mutations signaling cause to build leukemia and identify points of genetic predisposition, that can be used by "cocktail" treatments for drug resistance. The study is part of a journal issue focused on the resistance mechanisms in cancer.

"We need a"big picture"perspective", said Director author Thomas graves, Professor of medical and Molecular Pharmacology and researcher at the UCLA Crump Institute for molecular imaging, Jonsson Comprehensive Cancer Center and California NanoSystems Institute. "Understanding this complex network of events is crucial for the design of new molecular anti-cancer targeted at the same time target the primary mutation while prevented the development of the secondary, transfer of resistance mutations, and we have now additional tools, this to do."

Molecular targeted drugs inhibit the 'signal' consequences this espectro events. In many cases, resistance stems from secondary mutations replace or increasing cancer promoting original signal targeted by the drug. The future of molecular therapies, researchers say, relies on for multiple events at the same time, making it exponentially more difficult required for tumour cells, mutations, therapy escape to develop the effect of the drug. This corresponds to some anti-HIV drug cocktail therapies targeting the inhibition of several viral replication steps.

In their work, the UCLA team State-of-the-art uses technologies that simultaneously measure hundreds of signaling events in cancer cells. Try to learn more about how these events link to up to determine how to target the cancer cells. These new approaches to the complexity of the cancer cells include build sorting out a diagram wiring interconnections or "Crosstalk" in cancer cells, which help scientists to drugs overcome resistance.

Graves compares the target, a better roadmap, identifying the bypass routes of cancer cells used the inhibition by drugs to escape.

"We have the tourist information, but we determine the insiders know the taxi drivers know how the cell gets around traffic jams, rather than in a traffic jam stuck to," he said.

"Specifically, we use mass-spectrometry based Proteomics to measure the activity of the proteins in the teaching of the signals that cause cancer cells that uncontrollably grow, said Liudmilla Rubbi, researchers at the UCLA Crump Institute design helped the project."Then, we analyze the resulting large-scale, quantitative data with computational algorithms to identify the informative patterns within the network of events. "These patterns show us previously unknown interactions, which are essential for tumor hypercalcemia,."

The team these approaches in the study of leukemia applied by the BCR-ABL mutation, mutation, which successfully took the well-known drug targeting Glivec. In the development of drug resistant cases, it will be unmanageable in the clinic and are usually fatal. The researchers focused on two proteins, the clinical resistance mechanisms their studies.

An important issue originated from research participation of negative feedback mechanisms in cancer growth.

"The cell has to disable machines cancer promoting signal, but in general the effect of a mutation overwhelmed the feedback mechanisms," said Björn Titz, a postdoctoral scholar and co-author of the study. "The growth of the tumour requires the right balance between positive and negative signal tones and the State of the negative feedback mechanisms influences such as the cell to the shutdown of the initiating mutation of inhibitors such as Glivec specifically responds."

Leukaemia played a prominent role in the lead cancer research; Insight in who discovered leukemia research were regularly transferred to other types of cancer. The effects of Glivec, has for example the development of other molecular targeted anti-cancer drugs with similar measures supported.

The new roadmap also reading offers points for diagnosing patients cases that exposure can be naturally resistant to molecular targeted drugs before the drug. Hoping to address this problem graves's laboratory and the Crump Institute, new Microfluidic of diagnostic technologies for the production of genetic and signalling guide help measurements on tumor cells develop personalized medicine.

The research is by the national institutes of health, coordinating set Research University of California cancer, leukemia and Lymphoma Society and the German Academic Exchange service.

Source:
University of California - Los Angeles

See drug information on Gleevec.