Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Summary
Understanding tumor heterogeneity may be the next big quest in cancer science, as differences between cells within a tumor can have important consequences for how cancers are diagnosed and treated.


https://www.google.com/amp/s/www.mskcc. ... eity%3Famp

Last paragraph and discussion


"New Ideas for Therapy

In fact, research in Dr. Lowe’s lab has already uncovered new aspects of intra-tumor heterogeneity that potentially could inform treatment. For example, many studies of the problem have focused on identifying genetic differences between a person’s tumor cells. But in a recent report in Nature, Dr. Lowe and his co-workers showed that the heterogeneity is not always genetic.
Working in mouse models of T cell acute lymphoblastic leukemia (ALL), an often aggressive type of blood cancer, the researchers found that tumor cells, even genetically identical ones, may behave differently depending on where in the body they are located. This is because the cells’ ability to grow and survive is influenced by the tissue microenvironment — the noncancerous tissues, cells, and molecules that exist close to the tumor.
The findings could have implications for how T cell ALL tumors in different body sites respond to PI3-kinase inhibitors, a new class of drugs entering clinical trials for the disease. “It’s conceivable that these drugs might be effective against tumors in some body sites but not others, depending on differences in the local environment,” Dr. Lowe notes.
The good news, he adds, is that a number of other drugs currently in development work by targeting cells or molecules in a tumor’s surroundings, preventing these factors from supporting tumor growth. Scientists hope it will be possible to eradicate some difficult-to-treat tumors in the future by combining drugs such as PI3-kinase inhibitors, which act on tumor cells, with drugs that work on the tumor microenvironment.
But Dr. Lowe emphasizes that a lot more research is needed. “There’s so much we still don’t know about the biology of tumors and their microenvironment,” he says, “and we are only beginning to understand the clinical implications of tumor heterogeneity and how to deal with them.”

Paragraph 1 and 2

"All cancers arise as a result of somatically acquired changes in the DNA of cancer cells. That does not mean, however, that all the somatic abnormalities present in a cancer genome have been involved in development of the cancer. Indeed, it is likely that some have made no contribution at all. To embody this concept, the terms 'driver' and 'passenger' mutation have been coined.

A driver mutation is causally implicated in oncogenesis. It has conferred growth advantage on the cancer cell and has been positively selected in the microenvironment of the tissue in which the cancer arises. A driver mutation need not be required for maintenance of the final cancer (although it often is) but it must have been selected at some point along the lineage of cancer development shown in Fig. 1.

A passenger mutation has not been selected, has not conferred clonal growth advantage and has therefore not contributed to cancer development. Passenger mutations are found within cancer genomes because somatic mutations without functional consequences often occur during cell division. Thus, a cell that acquires a driver mutation will already have biologically inert somatic mutations within its genome. These will be carried along in the clonal expansion that follows and therefore will be present in all cells of the final cancer."


http://www.nature.com/nature/journal/v4 ... lback=true