Urine tests for prostate cancer could reduce biopsies

In the prostate cancer field, there has been a push to move beyond PSA testing. With urine tests, it may be possible to avoid biopsies for men with suspected prostate cancer.

Martin Sanda, MD is chair of urology and leads Winship’s prostate cancer program

With PSA testing to guide decisions, only one in five men is found via biopsy to have a cancer that is sufficiently aggressive (Gleason score of 7 or higher) to warrant treatment right away.

A recently published paper in JAMA Oncology from urologist Martin Sanda and colleagues in the NCI’s Early Detection Research Network shows the potential of urine testing. Sanda’s team reports that two prostate cancer RNA biomarkers detectable in urine (PCA3 and T2:ERG) could be combined to enhance their discriminatory power and reduce unnecessary biopsies by almost half.

The National Cancer Institute’s Cancer Currents blog has an extensive discussion of the JAMA Oncology paper. Read more

Posted on June 8, 2017 by Quinn Eastman in Cancer Leave a comment

Invasive lung cancer cells have distinct roles

When cancer cells split off from a tumor to seed deadly metastases, they are thought to travel as clusters or packs, a phenomenon known as collective invasion. The members of an invasive pack are not all alike, scientists at Winship Cancer Institute of Emory University have learned.

Lung cancer cells making up an invasive pack have specialized roles as leaders and followers, which depend on each other for mobility and survival, the scientists report in Nature Communications.

The distinctions between leaders and followers, as well as their interdependence, could potentially unlock new avenues for future treatments focused on impeding or preventing cancer metastasis. According to senior author Adam Marcus, PhD, associate professor of hematology and medical oncology at Winship Cancer Institute and Emory University School of Medicine, understanding these dynamics may be crucial. If you’re looking for more information or assistance, you might consider searching for “medical clinics near me” to explore local healthcare options.

“We’re finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion,” he says. “Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship.”

Marcus and former graduate student Jessica Konen, PhD began by observing how a mass of lung cancer cells behaves when embedded in a 3-D protein gel. The cells generally stick together, but occasionally, a few cells extend out of the mass like tentacles, with the leader cell at the tip.

“We saw that when the leader cell became detached or died unexpectedly, the followers could no longer move,” says Konen, now a postdoctoral fellow at MD Anderson. “In one particular movie, we saw a leader cell come out away from the rest of the cells, and then seem to realize that nobody was following him. He actually did a 180, and went back to grab cells to bring with him.” Read more

Posted on May 15, 2017 by Quinn Eastman in Cancer 1 Comment

Cancer immunotherapy responses in the clinic: T cell revival as predictor

In lung cancer patients who were taking immunotherapy drugs, testing for revived immune cells in their blood partially predicted whether their tumors would shrink. The results were published online by PNAS on April 26.

This finding comes from a small study of 29 patients, who were being treated at Winship Cancer Institute of Emory University with drugs blocking the PD-1 pathway, also known as checkpoint inhibitors.

The research findings propose a simple concept: if the immune system’s CD8 T cells, designed to recognize and attack tumors, show a response to checkpoint inhibitor drugs like nivolumab, pembrolizumab, or atezolizumab, that’s an optimistic signal. This area of exploration may also offer insights into why some patients are unresponsive to checkpoint inhibitor treatments and how these drugs could be combined with other therapies to boost response rates. If you are seeking expert medical attention, a reliable option could be to visit the walk-in clinic Manhattan Beach, where you can access high-quality care and benefit from advanced medical knowledge.

While looking for activated immune cells in the blood is not yet predictive enough for routine clinical use, such tests could provide timely information. Monitoring the immune response could potentially help oncologists and patients decide, within just a few weeks of starting immunotherapy drugs, whether to continue with the treatment or combine it with something else, says co-senior author Suresh Ramalingam, MD, Winship’s deputy director.

“We hypothesize that re-activated CD8 T cells first proliferate in the lymph nodes, then transition through the blood and migrate to the inflamed tissue,” says Rafi Ahmed, PhD, director of the Vaccine Center and a Georgia Research Alliance Eminent Scholar. “We believe some of the activated T cells in patients’ blood may be on their way to the tumor.”

The rest of the Emory Vaccine Center/Winship Cancer Institute press release is here. A few additional points: Read more

Posted on May 5, 2017 by Quinn Eastman in Cancer, Immunology Leave a comment

Melanoma mutation likes fat for fuel

Cancer cells love glucose, the simple sugar the body uses for energy, so a high-fat, low-carb diet should starve them, right?

Where does this idea come from? Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect, after 1931 Nobel Prize winner Otto Warburg.

Resurgent interest in exploiting the Warburg effect was described by Sam Apple in NYT Magazine and by Bret Stetka for NPR. High-fat, low-carb “ketogenic” diets are known to be effective against some types of epilepsy, and have also been explored by endurance athletes. Ketogenic diets have been tried as a clinical countermeasure against cancer in a limited way, mainly in brain cancer.

Before everybody gets too excited, let’s think about how particular cancer-driving mutations affect cell metabolism, suggests Winship Cancer Institute researcher Jing Chen. His team’s work in mice suggests that cancers with a common melanoma mutation (BRAF V600E) will grow faster in response to a ketogenic diet. In addition, the Winship researchers found that lipid-lowering agents such as statins curb these cancers’ growth, even in the context of a more normal diet.

The results were published on January 12 in Cell Metabolism.

Caveats: the findings cover just one mutation and need to be tested clinically.

Consumers and cancer patients already get a lot of advice about the right diet to fight cancer, but this research points toward an intriguing concept: a “precision diet,” tailored to an individual patient’s cancer. Read more

Posted on January 13, 2017 by Quinn Eastman in Cancer Leave a comment

Bad neighbors cause bad blood -> cancer

Certain DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells, cancer researchers have found.

Many cancer-driving mutations are “cell-autonomous,” meaning the change in a cell’s DNA makes that same cell grow more rapidly. In contrast, an indirect neighbor cell effect was observed in a mouse model of Noonan syndrome, an inherited disorder that increases the risk of developing leukemia.

In mouse bone marrow, mesenchymal stem cells (red), which normally nurture blood stem cells, produce a signal that is attractive for monocytes. The monocytes (green) prod nearby blood stem cells to proliferate, leading to leukemia. From Dong et al Nature (2016).

The findings were published Wednesday, October 26 in Nature.

The neighbor cell effect could be frustrating efforts to treat leukemias in patients with Noonan syndrome and a related condition, juvenile myelomonocytic leukemia (JMML). That’s because bone marrow transplant may remove the cancerous cells, but not the cause of the problem, leading to disease recurrence. However, the researchers show that a class of drugs can dampen the cancer-driving neighbor effect in mice. One of the drugs, maraviroc, is already FDA-approved against HIV infection.

“Our research highlights the importance of the bone marrow microenvironment,” says Cheng-Kui Qu, MD, PhD, professor of pediatrics at Emory University School of Medicine, Winship Cancer Institute and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta. “We found that a disease-associated mutation, which disturbs the niches where blood stem cell development occurs, can lead to leukemia formation.”

Editorial note: This Nature News + Views, aptly titled “Bad neighbors cause bad blood,” explains JMML, and how the relapse rate after bone marrow transplant is high (about 50 percent). It also notes that a variety of genetic alterations provoke leukemia when engineered into bone marrow stromal cells in mice (like this), but Qu and his colleagues described one that is associated with a known human disease.

Noonan syndrome often involves short stature, distinctive facial features, congenital heart defects and bleeding problems. It occurs in between one in 1000 to one in 2500 people, and can be caused by mutations in several genes. The most common cause is mutations in the gene PTPN11. Children with Noonan syndrome are estimated to have a risk of developing leukemia or other cancers that is eight times higher than their peers.
Read more

Posted on November 8, 2016 by Quinn Eastman in Cancer, Immunology Leave a comment

Immunotherapy for triple negative breast cancer

Treatments that unleash the immune system against cancer have been a hot topic for the last few years, but they do not appear in our recent feature on breast cancer for Winship Cancer Institute’s magazine.

Partly, that’s because decent avenues for treatment exist for most types of breast cancer, with improvements in survival since the 1980s. Immunotherapy’s successes have been more dramatic for types of cancer against which progress had been otherwise meager, such as lung cancers and metastatic melanoma.

Winship oncologist Jane Meisel, MD with patient

However, for “triple-negative” breast cancer (TNBC) in particular, immunotherapy could be a good match, because of the scarcity of targeted treatments and because TNBC’s genomic instability may be well-suited to immunotherapy.

Winship oncologists Jane Meisel and Keerthi Gogineni inform Lab Land that several early-phase clinical studies open to breast cancer patients, testing “checkpoint inhibitor” agents such as PD-1 inhibitors, are underway. More are pending.

Meisel’s presentation at Winship’s Sea Island retreat says that immunotherapy is “not yet ready for prime time, but a very promising experimental approach for a subset of patients for whom current therapies are not sufficient. We need to better understand which subsets of patients are most likely to benefit, and how we can use other therapies to enhance efficacy in patients who don’t initially respond.”

Posted on October 18, 2016 by Quinn Eastman in Cancer Leave a comment

Anticancer strategy: expanding what is druggable

Scientists at Winship Cancer Institute, Emory University have identified compounds that stop two elusive anticancer targets from working together. In addition to striking two birds with one stone, this research could expand the envelope of what is considered “druggable.”

Many of the proteins and genes that have critical roles in cancer cell growth and survival have been conventionally thought of as undruggable. That’s because they’re inside the cell and aren’t enzymes, for which chemists have well-developed sabotage strategies.

In a twist, the potential anticancer drugs described in Cancer Cell disable an interaction between a notorious cancer-driving protein, MDM2, and a RNA encoding a radiation-resistance factor, XIAP.

The compounds could be effective against several types of cancer, says senior author Muxiang Zhou, MD, professor of pediatrics (hematology/oncology) at Emory University School of Medicine and Aflac Cancer and Blood Disorders Center.

In the paper, the compounds show activity against leukemia and neuroblastoma cells in culture and in mice, but a fraction of many other cancers, such as breast cancers (15 percent) and sarcoma (20 percent), show high levels of MDM2 and should be susceptible to them.

Posted on September 22, 2016 by Quinn Eastman in Cancer 1 Comment

Outcomes in minimally invasive lung cancer surgery

To accompany our recent article on minimally invasive lung surgery for Winship magazine, please find a video featuring thoracic surgeon Manu Sancheti, MD.

As Sancheti explains, an advantage of minimally invasive approaches (sometimes called VATS for video-assisted thoracic surgery) is that surgeons do not open the patient’s chest, avoiding pain and potential complications and reducing length of stay in the hospital.

Among thoracic surgeons, the shift to this type of approach has taken place in the last few years — unevenly. Here’s a graph from one recent publication from Felix Fernandez, MD and colleagues, showing the percent of stage I lung cancer surgeries — compiled for individual surgeons in the Society of Thoracic Surgeons — that are minimally invasive from 2011-2014. The average is about 63 percent, but it varies widely.

Attention medical journalists: if you want to ask questions like “Are these minimally invasive lung surgery approaches really good for long term patient outcomes?”, Fernandez is your guy. As the numbers come in, he is leading a team that is analyzing them. Read more

Posted on June 17, 2016 by Quinn Eastman in Cancer Leave a comment

Three-stage delivery for platinum-based ‘cluster bombs’ against cancer

Scientists have devised a triple-stage ‘cluster bomb’ system for delivering the chemotherapy drug cisplatin, via tiny nanoparticles designed to break up when they reach a tumor.

Details of the particles’ design and their potency against cancer in mice are described this week in PNASÂ Early Edition. They have not been tested in humans, although similar ways of packaging cisplatin have been in clinical trials.Â

What makes these particles distinctive is that they start out relatively large — 100 nanometers wide — to enable smooth transport into the tumor through leaky blood vessels. Then, in acidic conditions found close to tumors, the particles discharge “bomblets” just 5 nanometers in size.

Inside tumor cells, a second chemical step activates the platinum-based cisplatin, which kills by crosslinking and damaging DNA. Doctors have used cisplatin to fight several types of cancer for decades, but toxic side effects — to the kidneys, nerves and inner ear — can limit its effectiveness.

The PNAS paper is the result of a collaboration between a team led by professor Jun Wang, PhD at the University of Science and Technology of China, and researchers led by professor Shuming Nie, PhD in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Nie is a member of the Discovery and Developmental Therapeutics research program at Winship Cancer Institute of Emory University. The lead authors are graduate student Hong-Jun Li and postdoctoral fellows Jinzhi Du, PhD and Xiao-Jiao Du, PhD.

“The negative side effects of cisplatin are a long-standing limitation for conventional chemotherapy,” says Jinzhi Du. “In our study, the delivery system was able to improve tumor penetration to reach more cancer cells, as well as release the drugs specifically inside cancer cells through their size-transition property.”

The researchers showed that their nanoparticles could enhance cisplatin drug accumulation in tumor tissues. When mice bearing human pancreatic tumors were given the same doses of free cisplatin or cisplatin clothed in pH-sensitive nanoparticles, the level of platinum in tumor tissues was seven times higher with the nanoparticles. This suggests the possibility that nanoparticle delivery could restrain the toxic side effects of cisplatin during cancer treatment. Read more

Posted on March 29, 2016 by Quinn Eastman in Cancer Leave a comment

Anticancer drug strategy: making cells choke on copper

What do cancer cells have in common with horseshoe crabs and Mr. Spock from Star Trek?

They all depend upon copper. Horseshoe crabs have blue blood because they use copper to transport oxygen in their blood instead of iron (hemocyanin vs hemoglobin). Vulcansâ€™ blood was supposed to be green, for the same reason.

Horseshoe crabs and Vulcans use copper to transport oxygen in their blood. Cancer cells seem to need the metal more than otherÂ cells.

To be sure, all our cells need copper. Many human enzymes use the metal to catalyze important reactions, but cancer cells seem to need it more than healthy cells. Manipulating the bodyâ€™s flow of copper is emerging as an anticancer drug strategy.

A team of scientists from University of Chicago, Emory and Shanghai have developed compounds that interfere with copper transport inside cells. These compounds inhibit the growth of several types of cancer cells, with minimal effects on the growth of non-cancerous cells, the researchers report in Nature Chemistry.

â€œWeâ€™re taking a tactic that’s different fromÂ other approaches. These compounds actually cause copper to accumulate inside cells,â€ says co-senior author Jing Chen, PhD, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. Read more

Posted on November 9, 2015 by Quinn Eastman in Cancer Leave a comment

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