Scientists at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) report today the development of new models to study molecular characteristics of tumors of the lung and pancreas that are driven by mutations in a gene named NTRK1. 

In healthy bodies, NTRK1 has critical functions in the development of nerve cells, particularly those that send signals to the brain about pain, temperature, and touch. In some cancers, these powerful genes malfunction to send signals to cells, instructing them to grow constantly.

The study, published in the journal Cell Reports, was led by Martin McMahon, PhD, senior director of preclinical translation at HCI and professor of dermatology at the U of U, and Aria Vaishnavi, PhD, a postdoctoral fellow in McMahon's lab. McMahon's team focuses on cell-cell communication, like the signaling promoted in some cancers by NTRK1.

One way to examine this experimentally is to devise a way to model human cancers in mice. This process produces a new tool, a "mouse model," which allows scientists to analyze in a laboratory setting how a cancer develops, how it behaves over time, and to test potential new drugs and treatment targets. The researchers hope the new NTRK1 mouse models reported today will accelerate progress toward finding more effective treatments for patients with NTRK1-driven lung and pancreas cancers.

A conversation with Ignacio Garrido-Laguna, MD, PhD, a physician-scientist at HCI, associate professor of internal medicine at the U of U, and director of the HCI Phase I Clinical Research Program, inspired the idea for this study. Garrido-Laguna was caring for a pancreatic cancer patient who was participating in a clinical trial at HCI (NCT02568267). The patient's tumor had a mutation in NTRK1 and then had a remarkable response to the NTRK1 inhibitor drug being evaluated. Hence, it made sense to Garrido-Laguna and McMahon that the response might be related to inhibition of the mutated NTRK1.

McMahon posited that if NTRK1 signaling was responsible, disruption of that signaling might be beneficial. "Pancreatic cancers have proven to be a particularly recalcitrant to treatments, so we wanted to thoroughly evaluate such a dramatic response as we work to identify new potential treatments for this disease," said McMahon. Moreover, since the responses to the NTRK1 inhibitors are often short-lived, McMahon and colleagues wanted to design new combination therapies that prevented the onset of lethal drug resistance.

Breast Cancer patients are 60 percent more likely to die of cancer after surviving a heart attack, a new study finds.

Led by researchers at NYU Grossman School of Medicine, the study shows how heart attacks, by blocking blood flow through arteries, trigger a specific, pro-cancer immune reaction.

Designed by evolution to attack invading bacteria and viruses, the immune system also recognizes cancer cells as abnormal and worthy of attack, say the study authors. But heart attack, along with other blood flow-reducing events like stroke and heart failure - were found to come with changes to immune cells that rendered them less able to respond to tumors.

Published online in Nature Medicine, the analysis of more than 1700 early-stage breast cancer patients found that those who also experienced heart attack, stroke, or heart failure had a greater risk than those that did not of cancer recurrence, cancer spread, and of dying from breast cancer.

The new work also found that mice with breast cancer saw a two-fold increase in tumor volume over 20 days after ligation (cutting off) of blood flow in the coronary artery, which simulated a heart-attack, when compared to mice with cancer but normal blood flow.

"By blunting the immune system's assault on cancer cells, a heart attack appears to provide an environment that enables tumor growth," says corresponding author Kathryn Moore, PhD, the Jean and David Blechman Professor of Cardiology, and Director of the Cardiovascular Research Center at NYU Langone Health. "While further studies will be needed, our results provide support for the aggressive clinical management of cardiovascular risk factors, not only to reduce risk of cardiovascular disease, but possibly breast cancer progression."

As one in eight American women will develop breast cancer during their lifetimes, and with nearly three million breast cancer survivors in the United States, the need for a better understanding the interplay between cancer and cardiovascular disease is urgent, adds Moore.

Patients who already used opioids, sedatives or antidepressants prior to colorectal surgery may experience significantly more complications post-surgery.  The study examined 1,201 patients 18 years of age and older who underwent colorectal resection for any indication other than trauma at UK HealthCare. Of these patients, roughly 30% used opioids, 28% used antidepressants and 18% used sedatives, all legally prescribed by a doctor pre-operatively.

Patients on any of these medications showed an increase in several common complications post-surgery, including infections, prolonged intubation, longer length of stay, readmissions, respiratory failure and even mortality. These problems were particularly pronounced in patients who regularly used opioids prior to surgery.

The preoperative use of opioids, sedatives and antidepressants is on the rise in the U.S. Though the current opioid crisis has raised awareness for limiting opioid use, many patients still receive opioids for pain management, and finding the right balance of medication is an ongoing issue for many patients and doctors. Patients with anxiety disorders or other mental health issues often receive sedatives or antidepressants.

As people age, cancer becomes an increasing health concern. Solid cancer tumors are cancers that don't affect the blood and instead form tumors, or growths of abnormal cells in certain parts of the body. These solid cancer tumors mainly impact people who are 65 and older.

If you or an older loved one is diagnosed with cancer, many different factors come into play to guide treatment choices. However, leading geriatric oncologists (specialists who treat cancer in older adults) say that, perhaps surprisingly, age is not necessarily one of them. Recently, leaders in the field emphasized that being older, on its own, does not necessarily mean that surgical treatment is not an option for you.

Older patients with cancer may not receive the same treatment as younger adults. The reasons for this are unclear and may include the fact that surgical oncologists fear a higher risk of poor outcomes for older cancer patients following surgery. They may be uncertain about how surgery will affect an older patient's survival and quality of life. But since long-term outcomes after surgery for older adults with cancer have not been well-studied, we don't know whether such concerns are justified.
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Fortunately, a screening tool exists that may help surgical oncologists and other physicians decide which patients might face complications after surgery. The "Preoperative Risk Estimation for Onco-Geriatric Patients" (or PREOP) risk score uses several easy-to-administer tests and can be given to people before surgery. The risk score includes a nutritional risk score to make sure you aren't malnourished and a test called Timed Get Up and Go (TUG). In this simple test, you are timed getting out of a chair, walking 10 feet, and sitting back down again.

Cancer care and management is a stressful and distressing time for patients and families at the best of times - with COVID-19 the challenges become even more monumental.  However, over the years we have come across the most remarkable stories of cancer patients who have overcome adversity to continue full and active lives. Below is a list of links for advice on cancer care during the pandemic that we hope you will find useful.
 
Cancer and Coronavirus (COVID-19). MacMillan Cancer Support

Coronavirus and COVID-19: What People With Cancer Need to Know. Cancer.Net 
 
Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal. National Comprehensive Cancer Network  
 
Cancer guidelines during the COVID-19 pandemic. The Lancet, Oncology 
 

One of the most frequent problems when treating cancer is that the tumours develop resistance to therapies, that is to say, at some point, treatments cease to be effective in stopping tumour growth. This is especially relevant in patients with aggressive diseases such as pancreatic cancer or patient with metastases, who for this reason often undergo frequent changes in treatment. Now, a study led by the Spanish National Cancer Research Centre (CNIO) in collaboration with researchers from the Weill Cornell Medicine Center and Pfizer Inc. (United States), proposes a novel combined approach to avoid pancreatic cancer resistance to chemotherapy, and thus achieve the elimination of these tumour cells effectively. The work will be published in the journal Cancer Cell.

Effective therapies in breast cancer
One of the characteristics of cancer is the alteration of the cell cycle, that is, the alteration of normal activity related to cell growth, maturation and death. The molecules CDK4 and CDK6 are involved in the uncontrolled cell growth, which ends up generating a tumour mass.

In recent years, drugs have been developed that inhibit the action of CDK4 and CDK6 and are very effective in stopping the growth of advanced breast cancer. Their clinical use, in combination with hormone therapy, has been approved in the United States since 2015 and in Europe since 2017 for patients with this type of cancer. The success of this combination has made it the standard treatment for these patients. However, until now it was not clear if these benefits could be extended to other types of cancer.

"A problem with CDK4/6 inhibitors is a consequence of their mechanism of action that prevents tumour cells from multiplying," explains Marcos Malumbres, Head of the CNIO Cell Division and Cancer Group and principal investigator of the project. "Most of the current chemotherapies -involving, for example, platinum or taxol derivatives-, act only on tumour cells that are dividing. Therefore, if we inhibit CDK4/6 and thus prevent these cells from dividing, we prevent chemotherapies from working properly. For this reason, until now it was believed that we could not combine CDK4/6 inhibitors with classical chemotherapy."
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Not at the same time, but after
During her predoctoral work at the CNIO, researcher Beatriz Salvador decided to design a new strategy in which CDK4/6 inhibitors would be used not at the same time as chemotherapy, but after chemotherapy to prevent the recovery of tumour cells. The results of the study show that administering CDK4/6 inhibitors after the drugs commonly used against various metastatic tumours prevents tumour cells from resisting these treatments and growing again after chemotherapy.

Chemotherapy used to shrink a tumor before surgery, called neoadjuvant chemotherapy, is becoming more common in many cancers, including stage II and III rectal cancer. However, the chemotherapy regimens FOLFOX and CapeOx used in this setting come with significant side effects, to the degree that many patients are unable to complete the recommended schedule. A University of Colorado Cancer Center study presented at the 2020 Gastrointestinal Cancers Symposium shows they may not have to: A small study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

"I think we need bigger studies to explore less intensive therapy - maybe lower doses, maybe a shorter course of treatment - to see what is the optimal dosing prior to surgery," says Ashley E. Glode, PharmD, assistant professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences, and the study's first author.

In some cancers, a tumor may be entwined with nearby organs and blood vessels to the point that surgery is not initially an option. Most patients with locally advanced rectal cancer are surgical candidates, but chemotherapy used to shrink a tumor prior to surgery has been associated with more successful surgeries and a lower rate of cancer recurrence. As a high-volume center for the treatment of these cancers, University of Colorado Cancer Center oncologists including Christopher Lieu, MD, noticed that patients who were unable to complete the recommended course of neoadjuvant chemotherapy seemed to have similar or even better outcomes than patients receiving the full dose, prompting the current study.

"We do all sorts of supportive care options to help keep patients on these therapies at the recommended, high doses. But based on our observations and on this early study, we're starting to talk about having less hesitancy to drop the drug or at least decrease the dosing," says Lieu, who is CU Cancer Center's interim associate director for clinical research.

Of the 48 patients included in the study, only 12.5 percent were able to tolerate the full dose of chemotherapy. Due to side effects, zero of six patients taking the regimen CapeOx completed the recommended dose.

Proton therapy leads to significantly lower risk of side effects severe enough to lead to unplanned hospitalizations for cancer patients when compared with traditional radiation, while cure rates between the two groups are almost identical. The findings come from an expanded analysis of the largest review of its kind, performed by researchers in the Perelman School of Medicine at the University of Pennsylvania, to evaluate whether or not patients undergoing radiation therapy at the same time as chemotherapy experienced serious adverse events within 90 days. Researchers found proton therapy reduces the relative risk of these side effects by two-thirds.

"This is exciting because it shows that proton therapy offers a way for us to reduce the serious side effects of chemo-radiation and improve patient health and wellbeing without sacrificing the effectiveness of the therapy," said the study's lead author Brian Baumann, MD, an adjunct assistant professor of Radiation Oncology at Penn and an assistant professor of Radiation Oncology at Washington University School of Medicine in St. Louis.

Proton therapy has a few key differences from traditional photon radiation. Photon radiation typically uses multiple x-ray beams to deliver radiation to the tumor target but unavoidably deposits radiation in the normal tissues beyond the target, potentially damaging those tissues as the beam exits the body. Proton therapy is an FDA-approved alternative radiation treatment that directs positively charged protons at the tumor. They deposit the bulk of the radiation dose to the target with almost no residual radiation delivered beyond the target, reducing damage to surrounding healthy tissue and potentially reducing side effects.

For this study, researchers evaluated side effects including pain or difficulty swallowing, difficulty breathing, nausea, or diarrhea, among others. Researchers focused on grade-three effects or higher, defined as side effects severe enough for patients to be hospitalized. They evaluated data on 1,483 cancer patients receiving radiation and chemotherapy at the same time. Of these, 391 patients received proton therapy, while 1,092 underwent photon treatment. All patients had non-metastatic cancer and were undergoing treatment intended to be curative. Patients with brain cancer, head and neck cancer, lung cancer, gastrointestinal cancer, and gynecologic cancer treated with concurrent chemo-radiation were included.
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The primary outcome was whether or not patients experienced adverse side effects that were grade-three or higher within 90 days of treatment. In the proton group, only 11.5 percent of patients (45) did, compared to 27.6 percent of patients (301) in the photon group. A weighted analysis of both patient groups, which controlled for other factors that may have led to differences between the patient groups, found that the relative risk of a severe toxicity was two-thirds lower for proton patients compared to photon patients.

What if a metal that's already used to repair broken bones, straighten teeth and keep arteries from clogging could also be used to stop your cancer from spreading? New findings published in Nature Biomedical Engineering from scientists at Fred Hutchinson Cancer Research Center show for the first time that a piece of small, thin metal mesh loaded with cancer-fighting immune cells shrinks tumors in preclinical models of ovarian cancer.

"Cell therapies to fight cancer have had great success in blood cancers but haven't worked well with solid tumors," said lead author Dr. Matthias Stephan, a faculty member in the Fred Hutch Clinical Research Division. "Our findings take a significant step toward making cell therapies effective against solid tumors by showing that a thin metal mesh loaded with T cells engineered to fight ovarian cancer cleared tumors in 70% of the treated mice."

Solid tumors, including cancers of the breast, ovary and pancreas, have a variety of tactics to hide from and fight back against cancer-killing immune cells like CAR (chimeric antigen receptor) T cells. Simply injecting anti-cancer cells has not worked; they don't reach the tumor or if they do reach the cancerous cells, they tire out in trying to kill them and are then shed from the body.

Stephan designs materials that are safe in the body and can carry cancer-fighting cells to tumors. "In addition to minimizing side effects in patients, our ultimate goal is to make T-cell therapies faster and cheaper to make, and easier to deliver to patients." he said.

In a step toward that goal, Stephan's latest study loaded CAR T cells targeting ovarian cancer onto a porous, mesh-like metal film and then placed the film on tumors.

"This is not just a passive delivery device," Stephan said. "It's a release platform that triggers an expansion of CAR T cells that can overcome defenses that tumors make against the immune cells."

The researchers used thin, nearly translucent metal films made by Monarch Biosciences (MonarchBio), which helped fund the project. The films are 10 micrometers thick, which is 1 millionth of a meter, or about seven times thinner than the average width of a human hair. Made of nickel titanium, the film can safely be implanted within the body and is used in other medical devices.
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Viewed under a powerful microscope, the film has minuscule spaces that can be configured into different patterns. The spaces can be filled with drugs or other liquids and then implanted in the body, where the liquids ooze out and find their targets.

During spaceflight, astronauts experience similar physical stress as cancer patients undergoing treatments such as chemotherapy, immunotherapy, and targeted therapy. In a commentary published November 14 in the journal Cell, researchers suggest that by mimicking a NASA astronaut's schedule of exercising before, during, and after a mission, cancer patients could reduce the long-term impact their treatments often have on their bodies.
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"It was surprising when we looked at similarities between astronauts during spaceflight and cancer patients during treatment. Both have a decrease in muscle mass, and they have bone demineralization and changes in heart function," says senior author Jessica Scott, an exercise physiology researcher at the Memorial Sloan Kettering Cancer Center's Exercise Oncology Service. The similarities also extend to brain function: "Astronauts may get something called space fog, where they have trouble focusing or get a little forgetful. That's very similar to what some cancer patients experience, which is called chemo brain."

Despite similar symptoms, astronauts and cancer patients often receive very different advice on how to take care of their bodies. Astronauts are required to exercise prior to their mission while physicians monitor their cardiorespiratory fitness and other systems to develop a baseline level. The astronauts are then required to exercise during their mission utilizing special equipment made for working out in space. When they return to Earth, physicians continue to monitor the astronauts until their cardiorespiratory fitness and other systems return to their pre-mission baseline levels.

"That's completely backwards to how it is on Earth, where cancer patients may still be advised to rest in preparation for and during treatment and may have to ask permission to exercise from their physicians," says Scott.

But Scott and her team of researchers suggest that basic exercise such as walking on a treadmill could benefit cancer patients in the long term. Like astronauts preparing for spaceflight, cancer patients that are monitored using similar tests such as cardiorespiratory fitness could develop their own baseline levels prior to receiving treatment. Exercising during and after treatment could then potentially reduce the negative side effects of treatments such as heart problems.