Developing Drug Impairs Process Cancer Cells Use for Growth

It looks like this will be useful later on.

A drug discovered and advanced by The University of Texas MD Anderson Cancer Center’s Institute for Applied Cancer Science (IACS) and the Center for Co-Clinical Trials (CCCT) inhibits a vital metabolic process required for cancer cells’ growth and survival.

IACS-10759 is the first small molecule drug to be developed from concept to clinical trial by MD Anderson’s Therapeutics Discovery team, which includes IACS and the CCCT. Therapeutics Discovery is a unique group of clinicians, researchers and drug development experts working collaboratively to create new treatment options, including small molecules, biologics, and cell-based therapies.

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Metabolic reprogramming is an emerging hallmark of tumor biology where cancer cells evolve to rely on two key metabolic processes, glycolysis and oxidative phosphorylation (OXPHOS), to support their growth and survival. Extensive efforts have focused on therapeutic targeting of glycolysis, while OXPHOS has remained largely unexplored, partly due to an incomplete understanding of tumor contexts where OXPHOS is essential.

“Through a comprehensive translational effort enabled by collaboration across MD Anderson, we have identified multiple cancers that are highly dependent on OXPHOS,” said Marszalek.

This effort inspired the discovery and development of IACS-10759, a potent and selective inhibitor of OXPHOS. Its advancement to clinical trials was made possible by a multidisciplinary team of more than 25 scientists across Therapeutics Discovery.

“Through this collaborative, 18-month process, we identified and rapidly advanced IACS-10759 as the molecule for clinical development,” said Di Francesco. “We believe IACS-10759 will provide a promising new therapy for cancer patients.”

There’s No Amount of Alcohol, Sausage or Bacon That’s Safe, According to These Cancer Experts

It’s certainly something people should think more about.

No amount of alcohol, sausage or bacon is safe according to a new global blueprint on how to beat cancer.

Even small amounts of processed meats and booze increase the risk of a host of cancers outlined in World Cancer Research Fund (WCRF) guidelines updated every decade.

The respected global authority has unveiled a 10-point plan to cut your risk of getting cancer by up to 40%.

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Processed meats also cause people to be overweight which can trigger many more cancers.

But UK experts have disagreed with the draconian advice insisting the odd bacon sandwich “isn’t anything to worry about”.

The WCRF found boozing is directly linked to increased risk of six cancers and for the first time recommended sticking to water or unsweetened drinks.

Innovative Immunotherapy Approach Eliminates Woman’s Breast Cancer

Immunotherapy is valuable at reversing cancer outcomes, as shown in the past months with the cancer “vaccine” that eliminated tumors in mice and now this immunotherapy that worked when other approaches didn’t.

“We’ve developed a high-throughput method to identify mutations present in a cancer that are recognized by the immune system,” Dr. Rosenberg said. “This research is experimental right now. But because this new approach to immunotherapy is dependent on mutations, not on cancer type, it is in a sense a blueprint we can use for the treatment of many types of cancer.”

The new immunotherapy approach is a modified form of adoptive cell transfer (ACT). ACT has been effective in treating melanoma, which has high levels of somatic, or acquired, mutations. However, it has been less effective with some common epithelial cancers, or cancers that start in the lining of organs, that have lower levels of mutations, such as stomach, esophageal, ovarian, and breast cancers.

In an ongoing phase 2 clinical trial, the investigators are developing a form of ACT that uses tumor-infiltrating lymphocytes (TILs) that specifically target tumor cell mutations to see if they can shrink tumors in patients with these common epithelial cancers. As with other forms of ACT, the selected TILs are grown to large numbers in the laboratory and are then infused back into the patient (who has in the meantime undergone treatment to deplete remaining lymphocytes) to create a stronger immune response against the tumor.

A patient with metastatic breast cancer came to the trial after receiving multiple treatments, including several chemotherapy and hormonal treatments, that had not stopped her cancer from progressing. To treat her, the researchers sequenced DNA and RNA from one of her tumors, as well as normal tissue to see which mutations were unique to her cancer, and identified 62 different mutations in her tumor cells.

The researchers then tested different TILs from the patient to find those that recognized one or more of these mutated proteins. TILs recognized four of the mutant proteins, and the TILs then were expanded and infused back into the patient. She was also given the checkpoint inhibitor pembrolizumab to prevent the possible inactivation of the infused T cells by factors in the tumor microenvironment. After the treatment, all of this patient’s cancer disappeared and has not returned more than 22 months later.

“This is an illustrative case report that highlights, once again, the power of immunotherapy,” said Tom Misteli, Ph.D., director of CCR at NCI. “If confirmed in a larger study, it promises to further extend the reach of this T-cell therapy to a broader spectrum of cancers.”

Simple Lung Cancer Scans That Could Save Thousands of Lives a Year

Cancer can be exponentially easier to treat or cure when it’s caught early.

A new study found that fewer than 2 percent of heavy smokers in the U.S. get recommended lung cancer screenings, an imaging test that can catch tumors when they are small and potentially curable. The numbers fall far short of screening for other types of cancer, including mammograms and colonoscopies—both procedures that are much more uncomfortable than the CT scan used to detect tiny tumors in the lungs.

Lung cancer is the leading cause of cancer death in the U.S., killing an estimated 150,000 Americans each year. For the past five years, such groups as the U.S. Preventive Services Task Force and the American Society of Clinical Oncology have urged people aged 55 or older who have smoked a pack a day (or the equivalent) for three decades or more to get checked for early stage disease. Medicare, the U.S. government’s insurance program for the elderly, pays for the procedure. None of it has made an impact.

“It’s still truly abysmal,” said Danh Pham, chief fellow of hematology/oncology at the University of Louisville’s cancer center in Kentucky, who will present the findings at the ASCO cancer meeting next month in Chicago. “We would like to make this a true call to action, whether it’s for more education or more research, to know why this disparity exists for lung cancer.”

It took a while for public health officials to start recommending routine lung cancer screening, because of questions about its accuracy and its ability to make a difference once the disease was detected. Subsequent studies confirmed the benefits for the heaviest smokers, with the use of screening intended for those most vulnerable to tumors.

The researchers analyzed registry data for everyone who underwent lung cancer screening in 2016 and found that 141,260 of the 7.6 million people eligible, or 1.9 percent, received it. By comparison, from 60 percent to 80 percent of eligible people get screening for breast, cervical and colon cancer, said Bruce Johnson, president of the American Society of Clinical Oncology and chief clinical research officer at the Dana-Farber Cancer Institute in Boston.

The testing shortfall could stem from primary care doctors’ failure to refer high-risk patients to one of 1,800 approved centers nationwide which provide the service. Psychological issues could also play a role, including fear of being diagnosed with a disease that smokers are constantly reminded of, Pham said.

“It’s very difficult to get patients to have this conversation with their doctors because of the stigma,” he said. “People may not want to know if they have lung cancer because it could confirm they’ve made bad lifestyle choices.”

Lung cancer deaths exceed those from breast, colon, pancreas and prostate cancer combined. There are very compelling reasons to get screened, said Johnson.

“If you screened the entire population of the U.S. who fit the criteria for having smoked enough and being the appropriate age, which is about 8 million people, you could save about 12,000 lives a year,” he said. “The majority of lung cancers picked up are early stage,” and finding them before the malignant cells spread reduces the risk of dying by about 20 percent, he said.

Glyphosate is a Significant Public Health Threat — Doses Previously Considered Safe Now Shown as Harmful in New Study

Glyphosate (found in the dangerous Monsanto Roundup) is a carcinogen that’s now being shown to be harmful in other ways too. It shouldn’t be allowed to be used, and it has already contaminated such large amounts of food supplies.

A chemical found in the world’s most widely used weedkiller can have disrupting effects on sexual development, genes and beneficial gut bacteria at doses considered safe, according to a wide-ranging pilot study in rats.

Glyphosate is the core ingredient in Monsanto’s Roundup herbicide and levels found in the human bloodstream have spiked by more than a 1,000% in the last two decades.

The substance was recently relicensed for a shortened five-year lease by the EU. But scientists involved in the new glyphosate study say their results show that it poses “a significant public health concern”.

One of the report’s authors, Daniele Mandrioli, at the Ramazzini Institute in Bologna, Italy, said significant and potentially detrimental effects from glyphosate had been detected in the gut bacteria of rat pups born to mothers, who appeared to have been unaffected themselves.

“It shouldn’t be happening and it is quite remarkable that it is,” Mandrioli said. “Disruption of the microbiome has been associated with a number of negative health outcomes, such as obsesity, diabetes and immunological problems.”

Prof Philip J Landrigan, of New York’s Icahn School of Medicine, and also one of the research team, said: “These early warnings must be further investigated in a comprehensive long-term study.” He added that serious health effects from the chemical might manifest as long-term cancer risk: “That might affect a huge number of people, given the planet-wide use of the glyphosate-based herbicides.”

Artificial Mole as Early Cancer Detection in Development

For those of you who aren’t enthused about some of the other modern methods of cancer screenings, this artificial mole will possibly provide another avenue sometime in the next several years or so.

Alongside cardiovascular disease, cancer has become the top cause of death in industrialised countries. Many of those affected are diagnosed only after the tumour has developed extensively. This often reduces the chance of recovery significantly: the cure rate for prostate cancer is 32 percent and only 11 percent for colon cancer. The ability to detect such tumours reliably and early would not only save lives, but also reduce the need for expensive, stressful treatment.

Researchers working with Martin Fussenegger, Professor at the Department of Biosystems Science and Engineering at ETH Zurich in Basel, have now presented a possible solution for this problem: a synthetic gene network that serves as an early warning system. It recognises the four most common types of cancer — prostate, lung, colon and breast cancer — at a very early stage, namely when the level of calcium in the blood is elevated due to the developing tumour.

The early warning system comprises a genetic network that biotechnologists integrate into human body cells, which in turn are inserted into an implant. This encapsulated gene network is then implanted under the skin where it constantly monitors the blood calcium level.

As soon as the calcium level exceeds a particular threshold value over a longer period of time, a signal cascade is triggered that initiates production of the body’s tanning pigment melanin in the genetically modified cells. The skin then forms a brown mole that is visible to the naked eye.

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The researchers used calcium as the indicator of the development of the four types of cancer, as it is regulated strongly in the body. Bones serve as a buffer that can balance out concentration differences. However, when too much calcium is detected in the blood, this may serve as a sign for one of the four cancers.

“Early detection increases the chance of survival significantly,” says Fussenegger. For example, if breast cancer is detected early, the chance of recovery is 98 percent; however, if the tumour is diagnosed too late, only one in four women has a good chance of recovery. “Nowadays, people generally go to the doctor only when the tumour begins to cause problems. Unfortunately, by that point it is often too late.”

The implant also has an additional advantage: “It is intended primarily for self-monitoring, making it very cost effective,” explains the ETH professor.

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So far, this early warning implant is a prototype; the associated work recently published in the journal Science Translational Medicine is a feasibility study. The researchers have tested their early warning system in a mouse model and on pig skin. It functioned reliably during these tests. Moles developed only when the calcium concentration reached a high level.

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The concept of the “biomedical tattoo,” as Fussenegger describes this new finding, would also be applicable to other gradually developing illnesses, such as neurodegenerative diseases and hormonal disorders. In principle, the researchers could replace the molecular sensor to measure biomarkers other than calcium.

The Cancer “Vaccine” That Eliminated Tumors in Mice is Now Beginning Human Trials

What could be one of the most promising scientific advances of the 21st century thus far has just entered a new stage.

An injectable “vaccine” delivered directly to tumours in mice has been found to eliminate all traces of those tumours, cancer researchers have found – and it works on many different kinds of cancers, including untreated metastases in the same animal.

Scientists at Stanford University School of Medicine have developed the potential treatment using two agents that boost the body’s immune system, and a human clinical trial in lymphoma patients is currently underway.

“When we use these two agents together, we see the elimination of tumours all over the body,” said senior researcher, oncologist Ronald Levy.

“This approach bypasses the need to identify tumour-specific immune targets and doesn’t require wholesale activation of the immune system or customisation of a patient’s immune cells.”

Cancer immunotherapy is tricky. Because cancer cells are produced by the body, the immune system doesn’t see them as a threat the same way it sees invaders like viruses.

That’s why some cancer immunotherapy treatments focus on training the immune system to recognise cancer cells as a problem.

It’s an effective area of treatment, but one that often involves removing the patient’s immune cells from their body, genetically engineering them to attack cancer, and injecting them back in – a process that is both expensive and time-consuming.

The Stanford vaccine could be much cheaper and easier.

It doesn’t work like the vaccines you might be familiar with. Instead of a prophylactic administered prior to infection, the researchers gave it to mice that already had tumours, injecting directly into one of the affected sites.

“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumour itself,” Levy said.

“In the mice, we saw amazing, bodywide effects, including the elimination of tumours all over the animal.”

The vaccine exploits a peculiarity of the immune system. As a tumour grows, the immune system’s cells, including T cells, recognise the cancer cells’ abnormal proteins and move in to take care of business.

But cancer cells can accumulate mutations to avoid destruction by the immune system, and suppress the T cells, which attack abnormal cells.

The new vaccine works by reactivating these T cells.

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Of the 90 mice with lymphoma, 87 were completely cured – the treatment was injected into one tumour, and both were destroyed. The remaining 3 had a recurrence of the lymphoma, which cleared up after a second treatment.

The treatment was also effective on the mice genetically engineered to develop breast cancer. Treating the first tumour often, but not always, prevented the recurrence of tumours, and increased the animals’ lifespan, the researchers said.

The team then tested mice with both lymphoma and colon cancer, injecting only the lymphoma. The lymphoma was destroyed, but the colon cancer was not. This demonstrates that T cells in tumours are specific to that kind of tumour – so the treatment isn’t without limitations.

But it does mean that immunotherapy is possible without genetically engineering cells outside the body; or, as is the case with a previous vaccine, extracting cancer RNA, treating it, injecting it into the body, and applying an electric charge to deliver it to immune cells.

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Its efficacy is about to be tested, though. The clinical trial currently underway is expected to recruit 15 patients with low-grade lymphoma to see if the treatment works on humans.

If it’s effective, the treatment may be used in the future on tumours before they’re surgically extracted to help prevent metastases, or even prevent recurrences of the cancer.

“I don’t think there’s a limit to the type of tumour we could potentially treat, as long as it has been infiltrated by the immune system,” Levy said.

The research has been published in the journal Science Translational Medicine.