Researchers at The University of Texas MD Anderson Cancer Center looked at antibody drug conjugates (ADCs) based on alpha-amanatin as one solution. They found that ADCs, when aimed at a gene called POLR2A, are highly effective in mouse studies in treating colorectal cancer. The drug caused complete tumor regression and greatly reduced toxicity. ADCs allow for improved targeting of cancer cells, resulting in less impact on healthy cells.
Xiongbin Lu, Ph.D., associate professor of Cancer Biology, observed that when the common tumor suppressor gene, TP53 is deleted resulting in cancer growth, another nearby gene, POLR2A is also deleted. Normal cells have two copies of POLR2A and TP53 genes. Lu's study targeted cancers that had a single copy of both genes, representing 53 percent of colorectal cancers, 62 percent of breast cancers and 75 percent of ovarian cancers.
"POLR2A is an essential gene for cell survival, including cancer cells," said Lu. "Because there is only one copy, the cancer cells are more susceptible to suppression of this gene."
Lu's study was published in the April 22, 2015 issue of Nature.