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More Blood Pressure Medication Recalls Due To Cancer Concerns

You may want an MBA. But you want to avoid NMBA.

NMBA stands for N-Methylnitrosobutyric acid, something that you don’t want in your blood pressure medications. But alas, this probable carcinogen continues to appear in various medications at higher than acceptable levels.

The latest news is that Torrent Pharmaceuticals Limited is further expanding its recall of Losartan Potassium Tablets USP and Losartan Potassium/hydrochlorothiazide tablets, USP, according to the U.S. Food and Drug Administration (FDA). The FDA announcement includes five more lots of these medications. The additional lots add to the lots of blood pressure medications that have been recalled in the past 14 months or so.

In 2018 and 2019, it seems like news about potential cancer-causing contaminants in medications has become as repetitive as the lyrics “My Name Is” in Eminem’s song “My Name Is.” I’ve written about such news for blood pressure medications in November of last year, January of this year, and again March of this year. Then, just last week I covered impurities found in a common heartburn medication, ranitidine. Then, on Thursday, I added an update that Novartis was halting its distribution of ranitidine, the generic form of Zantac, until further testing could be done.

Today In: Innovation

As they say when you soil your pants, one time may be an accident but more than three times is a trend. It is time to take a closer look at how drugs are being manufactured, stored, and distributed and how such processes are being monitored. As I have mentioned before, making medications is not the same as making handbags. You don’t, at least you shouldn’t, eat your handbags. While a poorly-made handbag could lead to social embarrassment, a poorly-made medication can have much greater and even life-threatening implications.

The FDA is the main agency to protect you against fraudulent and contaminated medications. But the FDA currently may not have the funding and the resources to carefully check everything that every drug manufacturer and distributor is doing, especially when some of these operations are rapidly changing or occurring overseas.

For now, if you are taking blood pressure medications, or any medications for that matter, pay attention to FDA warnings and recall news. The FDA maintains a searchable listing of active product warnings and recalls. As a precautionary measure, you may want to search for a medication before starting it. You can also check with your pharmacist to make sure that your medication is not on a recall or warning list. Of course, if you do find that your medication has a warning or is being recalled, don’t just stop taking it. That can be like trying to return a parachute while you are using it. Check with your doctor first to determine your course of action.

Follow me on Twitter or LinkedIn. Check out my website.

I am a writer, journalist, professor, systems modeler, computational and digital health expert, avocado-eater, and entrepreneur, not always in that order. Currently, I am a Professor of Health Policy and Management at the City University of New York (CUNY), Executive Director of PHICOR (@PHICORteam), and Associate Professor at the Johns Hopkins Carey Business School. My previous positions include serving as Executive Director of the Global Obesity Prevention Center (GOPC) at Johns Hopkins University, Associate Professor of International Health at the Johns Hopkins Bloomberg School of Public Health, Associate Professor of Medicine and Biomedical Informatics at the University of Pittsburgh, and Senior Manager at Quintiles Transnational, working in biotechnology equity research at Montgomery Securities, and co-founding a biotechnology/bioinformatics company. My work involves developing computational approaches, models, and tools to help health and healthcare decision makers in all continents (except for Antarctica) and has been supported by a wide variety of sponsors such as the Bill and Melinda Gates Foundation, the NIH, AHRQ, CDC, UNICEF, USAID and the Global Fund. I have authored over 200 scientific publications and three books. Follow me on Twitter (@bruce_y_lee) but don’t ask me if I know martial arts.

Source: More Blood Pressure Medication Recalls Due To Cancer Concerns

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Dr. Luke Laffin, staff cardiologist in Preventive Cardiology and Clinical Specialist in Hypertension at Cleveland Clinic answers questions that patients often ask about taking high blood pressure medicines: types of medications, side effects, when to call the doctor, role of self-blood pressure monitoring (including how often), the best time to take blood pressure medications, and if there is a chance that patients can come off medications. He ends the program with three important points for patients with high blood pressure.

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Promising Blood Test Could Help to Predict Breast Cancer Recurrence

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Doctors have gotten much better at detecting and treating breast cancer early. Drug and chemotherapy regimens to control tumors have gotten so effective, in fact, that in some cases, surgery is no longer necessary. In up to 30% of cases of early-stage breast cancer treated before surgery, doctors can’t find evidence of cancer cells in postoperative biopsies. The problem, however, is that there is currently no reliable way to tell which cancers have been pushed into remission and which ones have not.

That’s where an easy identifier, like a blood test, could transform the way early stage breast cancer is treated. In a paper published in Science Translational Medicine, researchers led by a team at the Translational Genomics Institute (TGen), an Arizona-based nonprofit, report encouraging results on just such a liquid biopsy. Its test, called Targeted Digital Sequencing (or TARDIS), was up to 100 times more sensitive than other similar liquid-biopsy tests in picking up DNA shed by breast cancer cells into the blood.

Currently available ways of tracking breast cancer cells in the blood are most useful in people with advanced cancer. In those conditions, cancer cells litter the blood with fragments of their DNA as they circulate throughout the body to seed new tumors in other tissues like the bone, liver and brain. But in early-stage breast cancer, these cells are, by definition, scarcer.

To address the problem, the research team, which included scientists at Arizona State University, the City of Hope, Mayo Clinic, and the Cancer Research UK Cambridge Institute, developed a new way to pick up elusive cancer DNA. They genetically sequenced tumor biopsy tissue from 33 women with stage 1, 2, or 3 breast cancer, most of whom received drug or chemotherapy treatment prior to getting surgery to remove their tumors. By comparing the tumor sequence to the sequence from the patients’ normal cells, the scientists isolated potential mutations that distinguished the cancer cells and identified those that were most likely to be so-called “founder mutations”—genetic aberrations present in the original cancer cells and carried into the resulting tumor.

On average, each patient harbored about 66 such founder mutations. For each patient, the scientists combined the founder mutations to form a personalized assay, which could then be used to pick up signs of breast cancer DNA in blood samples. Combining a number of mutations together turned out to be a more sensitive way to detect tumor DNA than trying to pick up a single or a small number of mutations in an already small number of tumor DNA fragments present in the blood.

They combined this approach with a new strategy for amplifying the scarce tumor DNA found in a blood sample by preserving the size of these snippets and attaching unique molecular identifiers to them to make them more easily detectable.

At the start of the study, TARDIS was able to find tumor DNA in the blood samples of all the patients; other liquid biopsies for breast cancer currently in development have reported picking up 50% to 75% of the cancer cases.

After the pre-surgery treatment TARDIS detected circulating tumor DNA in the blood in concentrations as low as 0.003%, or 100-fold more sensitive than other tests being developed.

“This is an important advance,” says Dr. Debu Tripathy, professor and chair of the breast medical oncology department at the University of Texas MD Anderson Cancer Center, who was not involved in the study. “This test can help identify those with early stage breast cancer who may still have residual cancer in their body that may not be detectable with standard scans.”

That could help guide treatment, by, for example, determining which patients require closer monitoring for recurrent growths. Because the sequencing identifies the genetic mutations contributing to the tumor, the test could also help doctors to decide which targeted drug therapies, which are designed to address specific cancer mutations, to prescribe for their patients.

Most importantly, the test could help women whose tumors are effectively eliminated by their pre-surgery treatment to avoid an operation altogether since the blood test would reassure her and her doctor that no residual tumor DNA remained.

“If we could really know with a more accurate degree of certainty that you don’t have residual disease, it would be help in saying that you don’t need any more therapy [including surgery],” says Dorraya El-Ashry, chief scientific officer of the Breast Cancer Research Foundation. ”Conversely, if you still had residual disease, if there is information from the test that can pinpoint the next therapy, that would also be better.”

Muhammed Murtaza, co-director of the center for non-invasive diagnostics at TGen, says TARDIS needs to be tested in a larger group of breast cancer patients before it can be rolled out to doctors’ offices. His team is planning to study the test’s efficacy in about 200 breast cancer patients, in order to clarify exactly what levels of tumor DNA found in the blood are most likely to lead to recurrence. They are also exploring how modified versions of TARDIS could be applied to other cancers, like esophageal, colorectal, pancreatic and prostate.

There’s even encouraging precedent for this sort of a liquid biopsy. Doctors routinely rely on a blood test for chronic myeloid leukemia, for example, to track patients’ response to targeted drugs that treat specific mutations driving the cancer. “Applying this same technology to more common solid cancers like breast cancer is the new frontier,” says Tripathy.

By Alice Park

Source: https://time.com

 

World Cancer day 4 th Feb — Success Inspirers’ World

World cancer day is a day we should remember,It’s a day for taking action ! Cancer is a word.Not a sentence John Diamond This day is celebrated as World Cancer day,where in, the world becomes one,united to fight cancer epidemic. This day is a reminder and an attempt to bring an awareness of cancer,in terms […]

via World Cancer day 4 th Feb — Success Inspirers’ World

A Cure For Cancer: How To Kill A Killer – The Guardian

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Last month, the Nobel prize in medicine was awarded for two breakthrough scientific discoveries heralded as having “revolutionised cancer treatment”, and “fundamentally changed the way we view how cancer can be managed”. One of them went to a charismatic, harmonica-playing Texan named Jim Allison for his breakthrough advances in cancer immunotherapy. His discovery had resulted in transformative outcomes for cancer patients and a radical new direction for cancer research. And yet many cancer patients, and even some doctors, have hardly heard of cancer immunotherapy or refuse to believe it. Those who have struggle to make sense of the new menu of options and sort reasonable hope from overblown hype………..

Read more: https://www.theguardian.com/science/2018/nov/04/a-cure-for-cancer-how-to-kill-a-killer-revolutionary-immune-system-immunotherapy

 

 

 

 

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Eat These 7 Foods to Help Prevent Prostate Cancer – Natural Cures

Prostate cancer affects men more than any other kind of cancer. Almost 15% of men in the US suffer from it—a disproportionate number that could be significantly reduced. Some of the symptoms that accompany prostate cancer include: loss of bladder control, blood present in urine, and a burning sensation during urination. Studies show that a diet high in saturated fats, as well as being overweight increase the risk of prostate cancer.

In fact, more and more doctors are learning that a definite link exists between the foods we eat and the risk of cancer. These foods can be beneficial to anyone with a high risk of cancer:

1. Fresh Fish 2. Greens 3. Tomatoes 4. Coffee 5. Nuts 6. Pomegranates 7. Orange Vegetables Eating these foods can cut down on the risk of prostate cancer, but they can also have a positive effect on both a man’s waistline and his overall quality of life. It’s also important to note the presence of regular exercise reduces not only the risk, but also the degree of prostate cancer. Eat well and live well.

 

 

 

 

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How a 150 Year Old Drug Might Help Battle Cancer – Tim Newman

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There are a number of ways to attack cancer; one of the most commonly used is radiation therapy. Radiation works on tumors in two ways; firstly, it damages DNA and, secondly, it produces oxygen radicals that also harm cancer cells. However, when oxygen levels are low (hypoxia), the body produces fewer oxygen radicals, meaning that radiation therapy is less effective. Because cancer cells divide so quickly, they require more oxygen than healthy tissue. At the same time, blood vessels within tumors are often poorly constructed, making them less efficient…….

Read more: https://www.medicalnewstoday.com/articles/323384.php

 

 

 

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The DNA Detectives Hunting The Causes of Cancer – Kat Arney

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Halfway up a hill overlooking the Great Rift Valley in western Kenya are two graves. One of them is a few years old now, bristling with bushy shrubs stretching bright green leaves towards a cloudless sky. The other is a freshly dug bed of rough red dirt planted with a white wooden cross. They are the final resting places of Emily’s mother and father, who died within four years of each other. Still a young woman, Emily now looks after her family’s rural homestead near Iten – a town famed for churning out long-distance runners and playing host to Mo Farah’s training camps.

Read more: https://mosaicscience.com/story/dna-detectives-cancer-genomics-mutational-signatures-mutographs/

 

 

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Exercise & Cancer Care: A Physiotherapist’s Guide to Fitness During & After Treatment – Catherine Granger

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If you were diagnosed with cancer more than five or 10 years ago, you might have been told to rest and avoid physical activity.

Today, it’s a different story: we now know exercise benefits most people both during and after cancer treatment.

In May, Australian cancer experts launched a “world-first” position statement calling for exercise to be prescribed to all cancer patients as part of their routine treatment.

But how do you best keep physically active in the midst of illness, and later, remission?

Here are a few things to keep in mind when it comes to exercise in cancer care.

Exercise can alleviate side effects

While treatment pathways vary from person to person, cancer therapy (and cancer itself) can take a hefty toll on your physical and mental health.

Cancer-related fatigue is one of the most common side effects of cancer treatment and can occur at any stage of the disease. Other side effects include reduced fitness, muscle weakness, difficulty undertaking daily activities, as well as depression and anxiety.

Although some of these problems may begin before a cancer diagnosis, they are likely to be exacerbated during treatment.

The good news is that exercise can help to alleviate some of the side effects of cancer and its treatment, and improve outcomes for people with cancer.

Staying active helps to maintain or enhance your physical fitness, reduce fatigue, relieve mental distress and improve your overall quality of life.

Research shows exercise can help people with cancer tolerate aggressive treatments such as chemotherapy.

There is also data to suggest that in some types of cancer, such as breast, colon and prostate cancer, exercise may improve rates of survival.

Try a combination of cardio and weights

The are two types of exercise you need to focus on during (and after) cancer treatment: cardio exercise and resistance exercise.

Cardio exercise is all about getting your heart pumping and your whole body working. Think brisk walking, jogging, cycling, swimming and dancing.

Resistance exercise, on the other hand, is about strengthening your muscles. This can be done using weight machines, dumbbells, elastic bands or just gravity and the weight of your own body.

When it comes to cardio, 150 minutes of moderate intensity exercise per week is the goal. You might achieve this with 30 minutes of brisk walking or cycling (on an exercise bike) five times a week.

If you find 30 minutes in one session is too challenging, begin with a 10-minute brisk walk and slowly build your way up — either by extending the duration of your walk each time, or adding more walks into your day.

The intensity — or how hard you exercise — is important too. The easiest way to work out how intensely you’re exercising is by using the “walk and talk” test.

If you are walking for exercise, you need to be walking fast enough that you are getting a bit puffed (moderate intensity) — but not so fast that you can’t speak in full sentences (vigorous intensity).

Although vigorous intensity exercise gets your heart rate up (and requires only 75 minutes per week, compared to 150), we don’t recommend starting with this unless you are a very competent exerciser or have the support of a health professional.

When it comes to resistance training, research shows exercises should be done two or three times per week involving exercises that target the major muscle groups.

If you haven’t exercised for a long time, start off slow. And remember: when it comes to exercise, something is always better than nothing.

I’ve started exercising, but how do I stay motivated?

Staying motivated can be hard, especially on the days when you are busy running to and from hospital appointments, or sitting for hours in the hospital to receive chemotherapy.

It’s even harder on the days when symptoms like fatigue are at their worst.

The first thing to think about is what works for you. If you’re someone who likes tracking your own progress and striving to improve your fitness levels, measuring your daily step count might be a good option.

Watching how many steps you take each day and challenging yourself to reach a daily goal is a great way to keep motivated — and it helps you keep track of your daily activity.

If you have a smartphone, most come with a free health app that can track your daily step count.

Another way to maintain motivation is to use an exercise diary; many people find it really satisfying to tick a box for each day they exercise. Plus, it gives you the chance to marvel at your efforts at the end of each week.

While many people prefer to exercise alone, some people find it boring. If this is you, think about asking a friend to join you, or see if your community has a local walking group or exercise class for people with cancer.

What about after cancer, can I stop now?

No way! Keep it up. Or start again if you have stopped.

Exercise for people in remission — both immediately after treatment and in the long term — is really important. Surviving cancer means you are at risk of several other chronic diseases including diabetes and cardiovascular disease.

Evidence tells us that exercise helps prevent these diseases, plus a growing body of evidence suggests exercise has a role to play in preventing the cancer coming back.

Maintaining a healthy lifestyle after cancer is more important than ever.

If you are currently undergoing cancer treatment (or are due to start soon) and planning to exercise, it’s a good idea to speak with your GP first. They’ll be able to refer you to an exercise specialist with experience in cancer care, such as a physiotherapist or accredited exercise physiologist.

 

 

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7 Tips for Coping with Emotions During & After Cancer Treatment — So You’ve Got Acute Blood Cancer…Join The Club!

According to the Canadian Cancer Society, the incidence of developing cancer increases after 50 years old. While I don’t have enough statistical information to disagree, young adults are falling victim to cancer as well…and they are faced with a slew of challenges as a result. When I was in the hospital, I met a 31 […]

via 7 Tips for Coping with Emotions During & After Cancer Treatment — So You’ve Got Acute Blood Cancer…Join The Club!

Could Immunotherapy Lead the Way to Fighting Cancer – Robin Marantz

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In the morning of June 24, 2014, a Tuesday, Vanessa Johnson Brandon awoke early in her small brick house in North Baltimore and felt really sick. At first, she thought she had food poisoning, but after hours of stomach pain, vomiting and diarrhea, she called her daughter, Keara Grade, who was at work. “I feel like I’m losing it,” said the woman everyone called Miss Vanessa. Keara begged her to call an ambulance, but her mother wanted to wait until her husband, Marlon, got home so he could drive her to the emergency room. Doctors there took a CT scan, which revealed a large mass in her colon.

Hearing about the mass terrified her. Her own mother had died of breast cancer at the age of 56. From that point on, Miss Vanessa, then 40, became the matriarch of a large family that included her seven younger siblings and their children. Because she knew how it felt to have a loved one with cancer, she joined a church ministry of volunteers who helped cancer patients with chores and doctor visits. As she prepared meals for cancer patients too weak to cook for themselves, she couldn’t know that the disease would one day come for her, too.

The ER doctors told Miss Vanessa she wouldn’t get the results of follow-up tests—a colonoscopy and a biopsy—until after the July 4 weekend. She had to smile her way through her own 60th birthday on July 6, stoking herself up on medications for nausea and pain to get through the day.

At 9:30 the next morning, a doctor from the Greater Baltimore Medical Center called. He didn’t say, “Are you sitting down?” He didn’t say, “Is there someone there with you?” Later Miss Vanessa told the doctor, who was on the young side, that when he delivers gut-wrenching news by telephone, he should try to use a little more grace.

It was cancer, just as Miss Vanessa had feared. It was in her colon, and there also was something going on in her stomach. The plan was to operate immediately, and then knock out whatever cancer still remained with chemotherapy drugs.

Thus began two years of hell for Miss Vanessa and her two children—Keara, who is now 45, and Stanley Grade, 37—who live nearby and were in constant contact with their mother and her husband. The surgery took five hours. Recovery was slow, leading to more scans and blood work that showed the cancer had already spread to the liver. Her doctors decided to start Miss Vanessa on as potent a brew of chemotherapy as they could muster.

Every two weeks, Miss Vanessa underwent three straight days of grueling chemo, administered intravenously at her home. Keara and her two teenage sons came around often to help out, but the older boy would only wave at Miss Vanessa from the doorway of her bedroom as he rushed off to another part of the house. He just couldn’t bear to see his grandmother so sick.

Miss Vanessa powered on for 11 months, visualizing getting better but never really feeling better. Then, in July 2015, the doctor told her there was nothing more he could do for her.

“My mom was devastated,” Keara says. Keara told her mother not to listen to the doctor’s dire prediction. “I said to her, ‘The devil was a liar—we are not going to let this happen.’”

So Keara—along with Miss Vanessa’s husband, brother and brother’s fiancée—started Googling like mad. Soon they found another medical center that could offer treatment. But it was in Illinois, in the town of Zion—a name Miss Vanessa took as a good omen, since it was also the name of her 5-year-old grandson. In fact, just a few days earlier little Zion had asked his grandmother if she believed in miracles.

The family held a fund-raiser for Stanley to get on a plane to Chicago with his mother every two weeks, drive her to Zion and stay with her at the local Country Inn & Suites hotel for three days of outpatient chemotherapy. It felt like a replay of her treatment in Baltimore—worse, since the drugs were delivered in a hotel instead of in her bedroom, and the chemotherapy caused nerve damage that led to pain, tingling and numbness in Miss Vanessa’s arms and legs.

And then, in May 2016, the Illinois doctor, too, said there was nothing more he could do for her. But at least he offered a sliver of hope: “Go get yourself on a clinical trial.” Weeks later, desperate, Miss Vanessa and Keara grew hopeful about a treatment involving mistletoe. They attended an information session at a Ramada extolling the plant extract’s anti-cancer properties. But when they learned that it would cost $5,000 to enroll, they walked out dejected.

Finally, Miss Vanessa’s husband stumbled onto a website for a clinical trial that seemed legit, something underway at the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, just down the road from their home. This new treatment option involved immunotherapy, something markedly different from anything she had gone through. Rather than poisoning a tumor with chemotherapy or zapping it with radiation, immunotherapy kills cancer from within, recruiting the body’s own natural defense system to do the job. There are a number of different approaches, including personalized vaccines and specially engineered cells grown in a lab. (See “A Cancer Vaccine?” and “A DNA-Based Attack”)

The trial at Hopkins involved a type of immunotherapy known as a checkpoint inhibitor, which unlocks the power of the immune system’s best weapon: the T-cell. By the time Miss Vanessa made the call, other studies had already proved the value of checkpoint inhibitors, and the Food and Drug Administration had approved four of them for use in several cancers. The Hopkins researchers were looking at a new way of using one of those drugs, which didn’t work at all for most patients but worked spectacularly well for some. Their study was designed to confirm earlier findings that had seemed almost too good to be true.

“With the very first patient who responded to this drug, it’s been amazing,” says Dung Le, a straight-talking Hopkins oncologist with long dark hair and a buoyant energy. Most of her research had been in desperately ill patients; she wasn’t used to seeing her experimental treatments do much good. “When you see multiple responses, you get super-excited.”

Immunotherapy is poised to become the standard of care for a variety of cancers. The work being done now is forcing a reconsideration of basic tenets of clinical oncology—for instance, whether surgery should be a first line of treatment or should come after drugs like Keytruda.

Many questions still remain. Elizabeth Jaffee, a member of the “cancer moonshot” panel convened by then-Vice President Joseph Biden in 2016, says she’s conscious of the danger of overselling a treatment. While the effect of checkpoint inhibitors can be “exciting,” she says, “you have to put it in perspective. A response doesn’t mean they’re cured. Some may have a year of response,” but the cancer might start growing again.

When Miss Vanessa paid her first visit to Le in August 2016, the physician explained that not every patient with advanced colon cancer qualified for the trial. Investigators were looking for people with a certain genetic profile that they thought would benefit the most. It was a long shot—only about one person in eight would fit the bill. If she had the right DNA, she could join the trial. If she didn’t, she would have to look elsewhere.

About a week later, Miss Vanessa was in her kitchen, a cheery room lined with bright yellow cabinets, when her telephone rang. Caller ID indicated a Hopkins number. “I didn’t want anyone else to call you but me,” said the study’s principal investigator, Daniel Laheru. He had good news: her genes “matched up perfectly” with the criteria for the clinical trial. He told her to come in right away so they could get the blood work done, the paperwork signed and the treatment started. Miss Vanessa recalls, “I cried so hard I saw stars.”

The trial was part of a string of promising developments in immunotherapy—an apparent overnight success that was actually more than 100 years in the making. Back in the 1890s, a New York City surgeon named William Coley made a startling observation. He was searching medical records for something that would help him understand sarcoma, a bone cancer that had recently killed a young patient of his, and came upon the case of a house painter with a sarcoma in his neck that kept reappearing despite multiple surgeries to remove it. After the fourth unsuccessful operation, the house painter developed a severe streptococcus infection that doctors thought would kill him for sure. Not only did he survive the infection, but when he recovered, the sarcoma had virtually disappeared.

Coley dug deeper and found a few other cases of remission from cancer after a streptococcus infection. He concluded—incorrectly, it turned out—that the infection had killed the tumor. He went around promoting this idea, giving about 1,000 cancer patients streptococcus infections that made them seriously ill but from which, if they recovered, they sometimes emerged cancer-free. He eventually developed an elixir, Coley’s Toxins, which was widely used in the early 20th century but soon fell out of favor as radiation and then chemotherapy began to have some success in treating cancer.

Then, in the 1970s, scientists looked back at Coley’s research and realized it wasn’t an infection that had killed the house painter’s tumor; it was the immune system itself, stimulated by the bacterial infection.

In a healthy body, T-cells activate their weaponry whenever the immune system detects something different or foreign. This might be a virus, a bacterium, another kind of disease-causing agent, a transplanted organ—or even a stray cancer cell. The body continuously generates mutated cells, some of which have the potential to turn cancerous, but current thinking is that the immune system destroys them before they can take hold.

Once scientists recognized the cancer-fighting potential of the immune system, they began to look for ways to kick it into gear, hoping for a treatment that was less pernicious than chemotherapy, which often uses poisons so toxic the cure may be worse than the disease. This immune-based approach looked good on paper and in lab animals, and showed flashes of promise in people. For instance, Steven Rosenberg and his colleagues at the National Institutes of Health’s National Cancer Institute made headlines when they removed a patient’s white blood cells, activated them in the lab with the immune system component known as interleukin-2, and infused the cancer-fighting cells back into the patient in hopes of stimulating the body to make a better supply of cancer-fighting cells. Rosenberg ended up on the cover of Newsweek, where he was hailed for being on the cusp of a cancer cure. That was in 1985.

The FDA did approve interleukin-2 for adults with metastatic melanoma and kidney cancer. But immunotherapy remained mostly on the fringes for decades, as patients continued to go through rounds of chemotherapy and radiation. “We’ve been curing cancer in mice for many, many years . . . but the promise was unfulfilled for a very long time in people,” says Jonathan Powell, associate director of the Bloomberg-Kimmel Institute at Hopkins.

Meanwhile, Topalian is continuing to work with Hopkins experts in genetics, metabolism, bioengineering and other areas. One of her colleagues, Cynthia Sears, recently received a grant to study biofilms—the colonies of bacteria that grow in the colon and can either promote or prevent cancer growth. Sears is looking at how a particular “tumor microbial environment” affects the way a patient responds—or fails to respond—to cancer immunotherapy.

“The immune system is the most specific and powerful killing system in the world,” says Pardoll, summing up the state of immunotherapy in early 2018. “T-cells have an amazingly huge diversity, and 15 different ways to kill a cell. The basic properties of the immune system make it the perfect anti-cancer lever.” But science won’t be able to fully mobilize that system without the help of myriad specialists, all working from different angles to piece together the incredibly complex puzzle of human immunity.
Indeed, many cancer experts lost faith in the approach over the next decade. “Nobody believed in immunotherapy except our own community,” says Drew Pardoll, the director of the BKI. The lack of support was frustrating, but Pardoll says it did have one salutary effect: It made immunotherapy more collegial and less back-biting than a lot of other fields of science. “When you’re a little bit ostracized I think it’s just a natural part of human nature…to sort of say, ‘Well, look, our field is going to be dead if we don’t work together, and it shouldn’t be about individuals,’” Pardoll said. He calls the recent explosion of successes “sort of like Revenge of the Nerds.”

In keeping with this collaborative spirit, immunotherapy researchers from six competing institutions have formed a cover band known as the CheckPoints, which performs at the annual meeting of the American Society of Clinical Oncology and in other venues. The band’s harmonica player, James Allison of the M.D. Anderson Cancer Center in Houston, helped set immunotherapy on its current course with his work on checkpoint inhibitors in 1996, when he was at Berkeley. He was the first to prove that blocking the checkpoint CTLA-4 (shorthand for “cytotoxic T-lymphocyte antigen”) with an antibody would generate an anti-tumor response. As Pardoll puts it, once Allison demonstrated that first checkpoint system, “we had molecular targets. Before that, it was a black box.”

The checkpoint system, when it’s working as it should, is a simple one: invader is detected, T-cells proliferate. Invader is destroyed, T-cells are deactivated. If T-cells were to stay active without an invader or a rogue cell to fight, they could create collateral damage to the body’s own tissues. So the immune system contains a braking mechanism. Receptors on the surface of the T-cells look for binding partners on the surfaces of other cells, indicating that those cells are healthy. When these receptors find the proteins they’re looking for, they shut the T-cells down until they spot a new invader.

Cancer cells are able to do their damage partly because they co-opt these checkpoints—in effect, hacking the immune system by activating the brakes. This renders the T-cells impotent, allowing the cancer cells to grow unimpeded. Now scientists are figuring out how to put up firewalls that block the hackers. Checkpoint inhibitors deactivate the brakes and allow the T-cells to get moving again. This lets the body kill off the cancer cells on its own.

Suzanne Topalian, who is Pardoll’s colleague at the Bloomberg~Kimmel Institute (and also his wife), played a key role in identifying another way the immune system could be used to fight cancer. After working as a fellow in Rosenberg’s lab, she became the head of her own NIH lab in 1989 and moved to Johns Hopkins in 2006. At Hopkins, she led a group of investigators who first tested drugs blocking the immune checkpoint receptor PD-1—short for “programmed death-1”—and the proteins that trigger it, PD-L1 and PD-L2.

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