oncologywatch

Wodarz D. Use of oncolytic viruses for the eradication of drug-resistant cancer cells. J R Soc Interface. 2009 Feb 6;6(31):179-86. PMID: 18664430

Dominik Wodarz, professor of Ecology and Evolutionary Biology at UC-Irvine, writes on the theoretical possibility of some day using oncolytic viruses to eradicate drug-resistant cancer cells prior to treatment with targeted therapies such as imatinib. Although critical conditions necessary for experimental investigation have yet to be reached, Wodarz hopes the study will stimulate new avenues of research and thinking.

Wodarz developed his mathematical model working from a concept in population dynamics, apparent competition: 

“Even if two populations or two species do not directly compete with each other, the fitter species can drive the less fit species extinct if they are infected by the same pathogen. For example, if the growth rate of the drug-sensitive cancer cells is higher than that of the resistant cancer cells, then the resistant cells will be driven extinct if a virus can infect both cell populations. In the context of CML [chronic myeloid leukemia] therapy with the targeted drug imatinib, it has been reported that certain drug-resistant mutants have a reduced growth rate and are less fit than the drug-sensitive cells."

According to the model, when drug-resistance mutations are demonstrated to have a "fitness cost" compared with drug-sensitive cells in a cancer, a virus can be used to drive resistant cell clones toward extinction prior to drug therapy. Because both drug-resistant and drug-sensitive cancer cells share the virus, competition with the fitter drug-sensitive cells would drive the resistant cells extinct. Then drugs could be used to treat the cancer without the emergence of resistance. 

Currently no cancers meet the three conditions that must exist before the model can be tested: the existence of an efficient targeted drug therapy, a detailed knowledge of drug resistance mutations, and a feasible oncolytic virus.

[OncologyWatch directory of open-access oncology journals.]

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

technorati tags: targeted therapy

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Price ND, Foltz G, Madan A, et al. Systems biology and cancer stem cells. J Cell Mol Med. 2008 Jan-Feb;12(1):97-110. PMID: 18031300

A comprehensive review of the state of science regarding cancer stem cells (CSCs), a subset of cells found within tumors and hematological malignancies and theorized to be responsible for starting and maintaining cancer. The authors are from the Institute for Systems Biology, the Seattle Neuroscience Institute, and the Department of Chemical and Biomolecular Engineering & Institute for Genomic Biology at the University of Illinois, Urbana-Champaign.

From the conclusion:

"The identification and prospective isolation of CSCs from leukaemia and a number of solid tumours has spawned a new paradigm in cancer research. From the perspective of systems biology – with the goal of predictive, preventive, personalized, and participatory (P4) medicine – we envision increasingly global assessment of CSCs and their microenvironments (niche) at the level of complete transcriptome, proteome and epigenome, using empowering new high-throughput technologies. The resulting gene expression profile signatures of cancer stem cell would serve as more accurate indicatives for cancer diagnosis and prognosis. Emerging proteomic technologies employing MS and protein chip platforms would allow for identification of better cell-surface markers and their interaction with the resident stem cell niche and potential diagnostic markers from both body fluids and tumour tissues. Incorporating these data into biological networks will provide fundament insights into the biology of CSCs and their abilities for renewal and differentiation. These combined efforts will ultimately lead to new therapeutic strategy specifically targeting CSCs for unprecedented personalized cancer therapy."

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

Technorati tags:
oncology cancer systems biology

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Lichtman MA. Battling the hematological malignancies: the 200 years’ war. Oncologist. 2008 Feb;13(2):126-38. PMID: 18305057

A clearly written historical review and perspective on current research by Marshall Lichtman of the University of Rochester Medical Center.

Professor Marshall applies a systems approach to drug development, employing a nuanced interpretation of the imatinib (Glivec) story as a case study:

"When one has stratified the blood cancers into phenotypes and genotypes, the number of patients amenable to a specific oncogene- or oncoprotein-targeted therapy becomes relatively small. This situation is unattractive for pharmaceutical companies that may need to invest hundreds of millions of dollars into the effort to develop a drug. For a pharmaceutical company, the greater the specificity of the drug, the fewer the number of future users. Today, most drugs can be used for several blood cancers and for cancers of other tissues. To move to more focused and, presumably, more effective and less toxic drugs, collaboration among governmental agencies, such as the National Institutes of Health, the pharmaceutical and biotechnology industries, and academic health centers (research-intensive medical schools, research institutes, research hospitals) needs to be further enhanced.

"There are incentives for companies to pursue drugs with an apparently small market. For example, the development of imatinib mesylate may have done more than advance the treatment of CML; it may have caused pharmaceutical companies to have second thoughts about developing new drugs for uncommon cancers. The pharmaceutical company involved (Ciba-Geigy, later Novartis) was looking for a drug to block a tyrosine kinase (platelet-derived growth factor receptor) potentially involved in atherosclerosis, a very large market, but was forced to aggressively manufacture imatinib mesylate because of the demands of patients with CML, a very small market, and in the end did (very) well by doing good, because of pricing, because of the fact that the drug is required indefinitely, and because of the drug’s ability to cause the remission of a gastrointestinal stromal tumor, which effectively doubled the target patient population. The latter event is another example of how drug development in the hematological malignancies continues to provide the path to therapy of other types of cancer."

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

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oncology cancer leukemia

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Brave M, Goodman V, Kaminskas E, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res. 2008 Jan 15;14(2):352-9. PMID: 18223208

Describes the Food and Drug Administration review of dasatinib for CML and Ph(+) ALL.

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oncology cancer chronic myeloid leukemia acute lymphoblastic leukemia

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Martin S, Ulrich C, Munsell M, et al. Delays in cancer diagnosis in underinsured young adults and older adolescents. Oncologist. 2007 Jul;12(7):816-24. PMID: 17673613

An important study with evidence that young people in the U.S. are likely to have a delay in cancer diagnosis because of inadequate health insurance, with consequent presentation of advanced stages of disease. From the introduction:

"Despite the advances in cancer diagnosis and treatment, older adolescents and young adults with cancer in the U.S., especially those in the 20–39 years age group, have not experienced the same survival prolongation or mortality reduction as their older and younger counterparts. Reasons for the failure to improve survival in this cohort may be related to delays in diagnosis, which are known to occur more frequently in cancer patients in this age group than in others. Also, the 18–24 years age group is both the most underinsured in the U.S. as well as the least likely to access health care, and the 25–34 years age group is the next most uninsured age group. The hypothesis of this study, therefore, was that a lack of health insurance is associated with delay in diagnosis in this age group." 

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oncology cancer brain and spinal cord cancers hodgkin disease leukemia lymphoma thyroid cancer

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