Antiangiogenic therapy and Cancer Stem Cells

Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia [Medical Sciences]

de Conley, S. J., Gheordunescu, E., Kakarala, P., Newman, B., Korkaya, H., Heath, A. N., Clouthier, S. G., Wicha, M. S.

Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenografts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. In vitro studies revealed that hypoxia-driven stem/progenitor cell enrichment is primarily mediated by hypoxia-inducible factor 1α. We further show that the Akt/β-catenin cancer stem cell regulatory pathway is activated in breast cancer cells under hypoxic conditions in vitro and in sunitinib-treated mouse xenografts. These studies demonstrate that hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs.

Celulas stem

Este es un articulo muy interesante

Is Bacterial Persistence a Social Trait?

Andy Gardner^1,2*, Stuart A. West², Ashleigh S. Griffin²

1 St John's College, Oxford University, Oxford, United Kingdom, 2 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom

The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such ‘persister’ cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes–a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a) cells are related (e.g. a single, clonal lineage); and (b) resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours.

Esto lleva a un blog a postular un posible parecido con las celulas stem, lo cual es muy interesante para el caso del cancer. Seria posible que las celulas stem cancerosas puedan tener este comportamiento? Es decir comportarse como stem por razones fenotipicas y no genotipicas y cambiar de un estado a otro. Esto explicaria el articulo de k. polyak que difiere de la mayoria y podria dar una teoria que cubriera todo.

Que se les ocurre hacer para comprobar esta hipotesis? Me gustaria que todos intentaran contestar (en comentarios). Es mas, lo hacemos obligatorio como un ejercicio. No se preocupen de poner algo que consideren tonto, solo asi se aprende.