The method for fighting cancer discussed by Gina Kolata in the passages quoted below, is similar to the method that led William Coley to first develop immunotherapy in the late 1800s. Coley searched the archives of his hospital, seeking any cases in which cancer seemed to have been spontaneously cured. When he had a few cases he looked for a common feature that might explain the cures. He found that in each case the patient had a severe viral or bacterial infection. When the patient’s immune system cured them of the infection, it also, as a desirable side-effect, cured them of the cancer. In the case of the rare ovarian discussed below, Dr. Levine hypothesizes that the common feature of the rare single-mutation cancers that can be cured by immunotherapy drugs, is that there is a mutated master gene that turns on and off other genes–creating an abnormal variation that somehow alerts the immune system of the presence of tumor cells that should be attacked. (The article quoted below is now over six years old–I wonder if in those six years Dr. Levine has found evidence to support, modify, or reject his hypothesis?) [My memory is foggy on this, but I think Steven Rosenberg may also have applied a similar method after he encountered a case of spontaneous cancer cure when he was working in a veteran’s hospital early in his career–see Rosenberg and Barry, 1992.]
Notice that the four patients only were cured because they had the courage and boldness to ask their oncologist to try a therapy that the standard protocol said would fail. And notice that the four patients only were cured because they had oncologists who had the courage and boldness to violate accepted protocols. Or maybe something besides courage and boldness explains the oncologists’ actions. Maybe the oncologists were practicing medicine in countries were hospitals, regulatory agencies, and health insurance companies did not exert as much pressure to follow the protocol as is exerted in the United States? (I wonder if there is enough information publicly available to check this possibility.)
Notice that instead of searching a dusty archive, Levine joined a patient ovarian cancer Yahoo discussion group. Patients were trying to be in control of their cancers, and unlike some doctors, Levine had the humility to think he could learn from what these activist patients reported. Citizen science is a resource to be used, not a distraction to be tamped down or ridiculed. [Amy Dockser Marcus defends citizen science, and gives an extended example, in her We the Scientists.]
Finally note that the method pursued by Coley and Levine can yield genuine actionable knowledge. Randomized double-blind clinical trials are not the only sources of knowledge.
Gina Kolata has written many thought-provoking articles. I hope to follow-up on this one sometime.
(p. D1) No one expected the four young women to live much longer. They had an extremely rare, aggressive, and fatal form of ovarian cancer. There was no standard treatment.
The women, strangers to one another living in different countries, asked their doctors to try new immunotherapy drugs that had revolutionized treatment of cancer. At first, they were told the drugs were out of the question — they would not work against ovarian cancer.
Now it looks as if the doctors were wrong. The women managed to get immunotherapy, and their cancers went into remission. They returned to work; their lives returned to normalcy.
. . .
“We need to study the people who have a biology that goes against the conventional generalizations.”
Four women hardly constitutes a clinical trial. Still, “it is the exceptions that give you the best insights,” said Dr. Drew Pardoll, who directs the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine in Baltimore.
The cancer that struck the young women was hypercalcemic small cell ovarian cancer, which typically occurs in a woman’s teens or 20s. It is so rare that most oncologists never see a single patient with it.
. . .
(p. D3) Women with this form of ovarian cancer were sharing news and tips online in a closed Yahoo group. Dr. Levine asked to become part of the group and began joining the discussions. There he discovered patients who had persuaded doctors to give them an immunotherapy drug, even though there was no reason to think it would work.
The women reported that their tumors shrank immediately.
. . .
Lung cancer, a genetic type of colorectal cancer and melanoma have huge numbers of mutations, and immunotherapy drugs often are successful in treating them. Cancers of the prostate, pancreas, breast, ovaries — and most other tumors — carry few mutations.
“These are the cancers that rarely respond,” Dr. Pardoll said.
The idea that the drugs might work against something like hypercalcemic ovarian cancer, which is fueled by just one genetic mutation, just made no sense.
“For the vast majority of cancers, there is an amazingly clean correlation between response to therapy and mean mutational load,” Dr. Pardoll said.
. . .
And then came a handful of women with a rare ovarian cancer. Oriana Sousa, 28, a psychologist in Marinha Grande, Portugal, was one of them.
She found out she had cancer in December 2011.
. . .
For the next four years, Ms. Sousa’s doctors tried to control the cancer, giving her rounds of chemotherapy, radiotherapy and surgery. But every time, new tumors emerged.
. . .
Things are different now. In 2015, she finally persuaded a doctor to give her an immunotherapy drug, nivolumab. Immediately, her tumors shrank and continued shrinking as she continued with the drug — so much that her doctors now say she has no evidence of disease. Life has returned to normal.
. . .
What saved her? Dr. Eliezer M. Van Allen, a cancer researcher at Dana-Farber Cancer Institute, has come across one clue.
He found that a gene mutated in kidney cancer was sort of a master regulator of other genes, controlling which were turned on and when. But the regulated genes were normal and did not produce proteins that the immune system might recognize as abnormal.
Nonetheless, patients responding to immunotherapy were the ones with the master gene mutation. “We saw this result and weren’t sure what to make of it,” he said.
Dr. Levine and his colleagues found the same phenomenon in patients with hypercalcemic ovarian cancers. One explanation, he and Dr. Van Allen said, is that the immune system may recognize that cells in which genes are erratically turning on and off are dangerous and should be destroyed.
“That is strictly hypothesis,” Dr. Levine cautioned.
For the full story see:
Gina Kolata. “Cured Unexpectedly.” The New York Times (Tuesday, February 20, 2018 [sic]): D1 & D3.
(Note: ellipses added.)
(Note: the online version of the story has the date Feb. 19, 2018 [sic], and has the title “Doctors Said Immunotherapy Would Not Cure Her Cancer. They Were Wrong.”)
The academic article co-authored by Dr. Levine that reports on the remission of a rare ovarian cancer in four women is:
The book by Marcus that I praise above is:
Marcus, Amy Dockser. We the Scientists: How a Daring Team of Parents and Doctors Forged a New Path for Medicine. New York: Riverhead Books, 2023.
Rosenberg’s encounter with a case of spontaneous cancer cure, that I mention above, can be found somewhere early in:
Rosenberg, Steven A., and John M. Barry. The Transformed Cell: Unlocking the Mysteries of Cancer. New York: G.P. Putnam’s Sons, 1992.