Harnessing a mushroom’s toxin to kill cancer

For some time, cancer researchers have considered alpha-amanitin, the toxin derived from “death cap” mushrooms, as a possible cancer treatment.

BY Ron Gilmore

For some time, cancer researchers have considered alpha-amanitin, the toxin derived from “death cap” mushrooms, as a possible cancer treatment. However, because of its penchant for causing liver toxicity, its potential as an effective therapy has been limited.

MD Anderson scientists looked at antibody-drug conjugates (ADCs) based on alpha-amanitin 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 combine powerful anticancer toxins linked to antibodies that 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, also is 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% of colorectal cancers, 62% of breast cancers and 75% of ovarian cancers.

“POLR2A is an essential gene for cell survival, including cancer cells,” said Lu. “Because there’s only one copy, the cancer cells are more susceptible to suppression of this gene.”

Lu’s study was published in Nature.

The discovery that POLR2A is deleted at the same time as TP53 means that therapies can more specifically target the genetic processes that allow cancer cells to thrive. Understanding that one copy of POLR2A can allow cancer to grow gives researchers a new target to hit. As it turns out, it can be suppressed by an ADC based on the mushroom toxin. Lu’s team tested alpha-amanitin because it was believed to specifically inhibit POLR2A.

More Stories From Conquest

Blood test could reveal pancreatic cancer earlier

By Ron Gilmore

MD Anderson named the top cancer hospital once again

By Julie Penne

Don’t let the sun catch you unprepared

E-cigarettes’ growing popularity underscores the need for regulation

MD Anderson collaborates on world’s first skull-scalp transplant

Doctors from MD Anderson and Houston Methodist Hospital have performed what is believed to be the world’s first partial skull and scalp transplant on a man whose treatment for a rare cancer of the scalp muscle left him with a deep head wound that wouldn’t heal.

Treating the cancer patient, not just the patient’s cancer

Palliative care and hospice care aren’t synonymous. Palliative care is a branch of medicine that helps patients deal with the physical side effects and emotional stress that come with cancer treatment and diagnosis. Meet the team that improves quality of life for patients.

The engines powering the moon shots

To better understand the Moon Shots Program, we offer a look at the 10 platforms that drive the research.

Jenna Arnold is reducing risk while leaving menopause for later

Like most parents, Jenna Arnold is doing all she can to ensure that she’ll live a long life to see her son, Jack, grow up and pursue his dreams. Women such as Arnold, who carry BRCA gene mutations, are participating in a first-in-the-nation MD Anderson clinical trial to reduce their risk of cancer while leaving menopause for later.

MD Anderson’s got talent

When they aren’t fighting cancer, these faculty and staff members are expressing themselves

Where in the world is MD Anderson?

The MD Anderson Cancer Network® allows the institution to collaborate with healthcare providers to provide MD Anderson’s model of multidisciplinary care to patients in the communities where they live.

The gift that’s giving life to discoveries

Ten years after San Antonio businessman Red McCombs and his wife, Charline, made a transformative $30 million gift to MD Anderson, their generosity is showing a big impact.