Posts Tagged ‘mathematical models’

New approaches to cancer therapy using mathematics

Reporter: Irina Robu, PhD

Our bodies are made up of trillions of cells grouped together to form tissues and organs such as muscles, bones, the lungs and the liver. Genes inside each cell tell it when to grow, work, divide and die. Usually, our cells follow these commands and we stay healthy. Nevertheless, occasionally the instructions get mixed up, triggers our cells to grow and divide out of control or not die when they should. As more and more of these abnormal cells grow and divide, they can form a lump in the body called a tumor.

Cancer therapy thrives in shrinking tumors and frequently fails in the long run; however, a small number of cancer cells are resistant to treatment. The cancer cells expand to fill the space left by the cells that were destroyed.  Using mathematical analysis and numerical simulations, Dr. Noble and Dr. Viossat, a mathematician at Université Paris-Dauphine proposed new approach to validate the concept of using a combination of biological, computational and mathematical models and they show how spatial constraints within tumors can be exploited to suppress resistance to targeted therapy.

Lately, mathematical oncologists have designed a new method to tackling this problem based on evolutionary principles. Known as adaptive therapy, this as-yet unproven strategy aims to stop or delay the failure of cancer treatment by manipulating competition between drug-sensitive and resistant cells. It uses relatively low doses and has the additional potential benefits of reducing side effects and enhance quality of life.

As a way to solve the problem, Dr. Noble and Dr. Viossat organized a workshop for mathematical modelers to determine the state of art of adaptive therapy, discuss future directions and foster collaborations. The virtual event was attended by one hundred persons who participated in more than twenty talks, interacting via the Sococo virtual meeting platform.

Dr. Noble plans to continue developing mathematical models to improve cancer treatment. His long-term objective is to project optimal treatment regimens for each tumor type and each patient.



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Preface to Metabolomics as a Discipline in Medicine

Author: Larry H. Bernstein, MD, FCAP


The family of ‘omics fields has rapidly outpaced its siblings over the decade since
the completion of the Human Genome Project.  It has derived much benefit from
the development of Proteomics, which has recently completed a first draft of the
human proteome.  Since genomics, transcriptomics, and proteomics, have matured
considerably, it has become apparent that the search for a driver or drivers of cellular signaling and metabolic pathways could not depend on a full clarity of the genome. There have been unresolved issues, that are not solely comprehended from assumptions about mutations.

The most common diseases affecting mankind are derangements in metabolic
pathways, develop at specific ages periods, and often in adulthood or in the
geriatric period, and are at the intersection of signaling pathways.  Moreover,
the organs involved and systemic features are heavily influenced by physical
activity, and by the air we breathe and the water we drink.

The emergence of the new science is also driven by a large body of work
on protein structure, mechanisms of enzyme action, the modulation of gene
expression, the pH dependent effects on protein binding and conformation.
Beyond what has just been said, a significant portion of DNA has been
designated as “dark matter”. It turns out to have enormous importance in
gene regulation, even though it is not transcriptional, effected in a
modulatory way by “noncoding RNAs.  Metabolomics is the comprehensive
analysis of small molecule metabolites. These might be substrates of
sequenced enzyme reactions, or they might be “inhibiting” RNAs just
mentioned.  In either case, they occur in the substructures of the cell
called organelles, the cytoplasm, and in the cytoskeleton.

The reactions are orchestrated, and they can be modified with respect to
the flow of metabolites based on pH, temperature, membrane structural
modifications, and modulators.  Since most metabolites are generated by
enzymatic proteins that result from gene expression, and metabolites give
organisms their biochemical characteristics, the metabolome links
genotype with phenotype.

Metabolomics is still developing, and the continued development has
relied on two major events. The first is chromatographic separation and
mass  spectroscopy (MS), MS/MS, as well as advances in fluorescence
ultrasensitive optical photonic methods, and the second, as crucial,
is the developments in computational biology. The continuation of
this trend brings expectations of an impact on pharmaceutical and
on neutraceutical developments, which will have an impact on medical
practice. What has lagged behind, and may continue to contribute to the
lag is the failure to develop a suitable electronic medical record to
assist the physician in decisions confronted with so much as yet,
hidden data, the ready availability of which could guide more effective
diagnosis and management of the patient. Put all of this together, and
we can meet series challenges as the research community
interprets and integrates the complex data they are acquiring.


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