target for metastatic cancer
Yale researchers have found genetic mutations that are potential drug targets for metastatic cancer, according to a study published Oct. 9 in Science.
In addition to providing a target for a drug that would inhibit the spread of cancer, the finding also could lead to early screening tests for tumors most likely to metastasize.
The leading cause of cancer deaths is metastasis, which is when cells from the original tumor travel to other parts of the body, forming new tumors. Cancer is often fatal when it has progressed to this stage.
The principal investigator of the study is Tian Xu, professor and vice chair of the Department of Genetics at the School of Medicine and an associate investigator for the Howard Hughes Medical Institute.
"The problem for researchers," he says, "is that it is hard to determine the genetic basis for metastasis because late-stage cancers cause a cascade of cell mutations, making it difficult if not impossible to determine which mutations cause the metastases."
To address this problem, Xu and a Yale graduate student, Raymond Pagliarini, generated tumors in fruit flies, or Drosophila melanogaster. Since the genes in fruit flies are remarkably similar to those in humans, results from genetic experiments on fruit flies have direct implications toward understanding human development, explains Xu.
Tumors resulting from a mutation in a gene called Ras, also commonly disrupted in human tumors, did not metastasize in the fly. The researchers then screened a large number of additional mutations to see which could make these tumors spread. Only a small number of mutations from the initial test group caused tumors to metastasize. Each of the new mutations affect cell-polarity maintenance, a process that is critical in allowing cells to communicate with their surroundings. But these mutations alone cannot cause metastases to form, note the researchers.
Xu and Pagliarini then surveyed a number of different early tumor-initiating mutations and found that only Ras mutations could cooperate with the cell polarity gene mutations to make tumors spread.
This concept, previously underappreciated, has major implications toward our understanding of why tumors of distinct origins have such different potentials for metastasis," Xu says.
"By finding common sets of gene mutations that can make a tumor metastasize, this guides us to specific biological processes that can be targeted by drugs to inhibit metastases," he explains. "It also implies that we may soon have a better ability to detect early on which tumors require the most intensive treatment to stop the progress of cancer."
-- By Jacqueline Weaver
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