New cancer drugs that trigger the immune system tumors are fashionable , getting credit for cure former President Jimmy Carter advanced melanoma and inspiring technology billionaire Sean Parker to pledge $ 250 million for cancer research. Behind the excitement, however, is the hard truth that these therapies work only in a minority of patients.
Now scientists are finding evidence of a solution in an unexpected place: Mayor, out of favor cancer treatments such as chemotherapy and radiation can make drugs last generation based on effective immunity against more cancers – even hard-treat ovarian and pancreatic tumors.
The growing body of research raises the possibility that it may not be necessary to invent new drugs to make significant progress against cancer. “If we only take the drugs we have and combine them in the right way, I think there is huge potential” to defeat more cases of cancer in remission, said Dr. Patrick Hwu of the MD Anderson Cancer Center in Houston.
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If the first successes to be a success in animal experiments and clinical trials currently underway dozens, patients would have more options and a better chance of real cure . Another advantage: radiation and generic chemotherapy are relatively cheap compared to new immuno-oncology drugs
Tumors disabled killer T cells of the immune system that can find and destroy certain. cancer cells. immunotherapy drugs work by preventing tumors using this tactic diverted. But if there is no T cells are milling around the tumor, first, the drugs do not help. It’s like playing the San Antonio Spurs of the NBA defensive player of the year Kawhi Leonard sitting on the bench, but then not get their own players past half field.
The trick, therefore, is to make tumors “cold” that ignore the T cells in the “hot” tumors that attract T. O cells, with the risk of torture metaphor, to get those last midcourt T cells. “If the T cells are not present, the question is, how do they exist?” Hwu said.
One answer: through chemotherapy or radiation. When these treatments of the old guard begin to destroy tumor cells, cells release molecules that can attract T cells to join in the attack. “They have the potential to prime the pump for immunotherapies,” said Dr. Gary Gilliland, a president of the Center for Cancer Research Fred Hutchinson in Seattle.
Biologists England recently got a hint of it. Researchers led by Frances Balkwill Queen Mary University of London compared 54 women with severe ovarian cancer who received standard chemotherapy (carboplatin or paclitaxel) before surgery and six that did not. In women treated with chemotherapy was not significantly greater activation of the class of T cells that attack cancer cells than in the other six, scientists he reported in June in Clinical Cancer Research. “There is a belief that chemotherapy suppresses the immune system, but weeks after treatment, a large number of T cells found in the tumor environment,” Balkwill said.
The mere fact that the T cells clearly is not enough; if it were, ovarian cancer would not be so lethal. In fact, it found Balkwill, surviving tumor cells were T cells incapacitating pullulan. However, immunotherapy such as ipilimumab pembrolizumab Merck and Bristol-Myers Squibb may prevent tumor cells to do that.
results Balkwill, therefore, suggest that a form of chemotherapy invented in the 1960s could leave 21 st century immunotherapies work against more types of cancer immunotherapies and the pairing with existing chemotherapies (which quickly become resistant cancers) could make each more effective. A cold ovarian cancer tumor could become a hot, T cells that attract one, for example, melanoma, against which immunotherapies have had some of its best results.
the radiation, which was first used against cancer at the turn of the 20th century, can also convert hot cold tumors. In study published in June, scientists led by the radiation oncologist Dr. Ralph Weichselbaum of the University of Chicago Medical Center found exactly that in mice with pancreatic cancer, which is known to be almost untreatable, so as not destroying tumors attract T cells. (The only immunotherapy have no effect on pancreatic cancer in people slowed tumor growth in only 8 percent of them.)
“We believe that radiation tumor turned cold in attracting T cells, while T cells immunotherapy remains to be disabled, “said Weichselbaum. “I think some cancers that are not now treated with radiation could be,” as long as immunotherapy follows.
“If only we take drugs we have and combine them in the right way, I think there is huge potential.”
Dr. Patrick Hwu, MD Anderson Cancer Center
Paul Mihocko a retired ironworker in Hyde Park, NY, it is living proof of the promise of that strategy. Happily he retired after working in many of the iconic bridges in the Hudson River, which was diagnosed with metastatic melanoma nine years ago after a lump was found in her right armpit. Although chemotherapy seemed to lead to cancer in remission, he returned in 2009.
Mihocko then offered for early clinical trial of ipilimumab in Cancer Center Memorial Sloan-Kettering in New York. Ipilimumab also worked for a few years, but while in the trial another tumor developed, over his heart.
“I was told obviously the IPI has stopped working,” Mihocko said.
He was referred to Dr. Chris Barker, a radiation oncologist at Sloan-Kettering. “. He said he was 90 percent sure I could get the tumor with radiation and the IPI was still in me,” said Mihocko – or at least the T cells to attack tumors had pumped appeared to be. But for some reason, the T cells are cancer cells. Mihocko enrolled in a clinical trial carried Barker. Was “cooked completely lost and exhausted” by radiation treatments twice a week for five weeks, Mihocko said, but “seemed to give a boost to the IPI, and the tumor disappeared.”
Now he is able to walk, play golf, and lawn mowing five-eighths-of-un-acre. “I realized I was about to leave,” he said. “I’m very lucky, that’s all.”
Luck helps, but Barker believes that other factors were also at work. “Radiation can make tumor cells more vulnerable to immunotherapy,” he said, even changing the way the tumor cells are the immune system; that would “make them a more attractive target to attack.” Barker is helping take several combination of radiotherapy studies with an immunotherapy, including one for metastatic melanoma and one for metastatic breast cancer , while other researchers are testing the combination of metastatic head and neck and metastatic colorectal cancer .
In M. D. Anderson, Department lung, head and neck cancer and one is running 36 clinical trials of combinations. There are dozens more trials in other centers of major academic cancer in the country, and “the big pharmaceutical companies are potentially looking all combinations out there,” said Hutch Gilliland, who oversaw the development of what is pembrolizumab when he was at Merck.
At the annual meeting of the American Association for Cancer Research in April, scientists presented more than a dozen studies of radiation or chemotherapy plus immunotherapy investigating. A year-old three-drug chemotherapy for cancer of the head and neck change those tumors in a way that should make them more vulnerable to immunotherapies, French scientists reported , while other researchers unveiled promising combinations for pancreatic cancer and non-small cell lung cancer .
With over 200 approved cancer drugs and more in the pipeline business, the number of possible combinations is essentially infinite, said Dr. Chris Boshoff, vice president of immuno- oncology at Pfizer. “We want to focus on those where you have a rational biological basis” for expecting to see a profit, he said. For example, Pfizer is test avelumab experimental immunotherapy (developed with Merck KGaA) in combination with doxorubicin chemotherapy in ovarian cancer and radiation for head and neck cancer.
Other cancer biologists think it makes sense to try many combinations as possible and see what works.
With the approach of see-what-sticks, Hwu of MD Anderson said, “you might get lucky, like a chimpanzee on a keyboard might get lucky and typing Hamlet, but I always think more science is better . ” The search for combinations has become so heated, however, that “many of them just put together combinations with minimal data” to support a particular couple.
One obstacle to the choice of effective combinations is that, traditionally, anticancer drugs and radiation have been tested in mice lacking an immune system, so that the human tumor transplanted in them (the standard design study) would not be rejected and ruin the experiment. As a result, there was no opportunity to see how drugs affect the ability of the immune system to attack the tumor.
“Consequently, we have a more detailed understanding of how chemotherapy and radiation affects the immune response,” said Dr. Sharma Padmanee M. D. Anderson. But now scientists are using mice with functional immune systems to fill gaps in their knowledge. If they do, cutting edge immuno-oncology drugs could get a big boost of cancer treatments often dismissed as primitive and ineffective. Call back to the future.
Correction :. An earlier version of this story misspelled the name of Dr. Chris Boshoff