Pancreatic cancer is nasty, sneaky and nearly impervious to the effects of chemotherapy, and its dispiriting five-year survival rate of 6% has budged not at all in decades. But researchers at the Salk Institute in California reported that they have found a way to unmask this stone-cold killer and render it vulnerable to standard cancer treatments.

Using a chemically modified version of vitamin D, the Salk scientists appear to have kicked open the doors to the vault within which pancreatic tumours flourish — in mice, at least. That exposes this most inexorable of cancers to the tender mercies not only of the immune system, but of chemotherapy as well.

In mice with pancreatic ductal adenocarcinoma, the addition of this vitamin D analog, called Calcipotriol, to chemotherapy prolonged survival by 57% over chemotherapy alone. Treated with a regimen of the cancer drug gemcitabine-plus-Calcipotriol, almost 3 in 10 of the mice in their experiments were considered “long-term” survivors: They lived an average of 53 days after treatment began, three to four times longer than those who got gemcitabine alone.

In the realm of pancreatic cancer research, that’s a first, said Salk Institute researcher Ronald Evans, senior author of the study, published in Cell last week. In research involving other types of cancers, the appearance of long-term survivors is “a sign you’re on the right track,” said Evans.

Even before the publication of the Salk team’s discovery, the US Food and Drug Administration gave the go-ahead to human trials on the Calcipotriol-plus-chemotherapy approach to treating pancreatic cancer. Early human trials to flesh out the safety and dosages of the adjuvant to cancer therapy are underway at University of Pennsylvania and at the Translational Genomics Research Institute in Phoenix.

The Salk team’s approach to attacking hard-to-reach cancers is novel. Instead of attacking cancer cells themselves, or trying to destroy the complex of supportive structure that grows up around a tumour, Evans said, his lab has looked for ways to genetically reprogram the microenvironment within which tumour cells grow unchecked.

In pancreatic cancer, that has meant finding a way to get the tumour to shed the “invisibility cloak” that grows up around it and makes it invisible to the immune system and immune to the effects of chemotherapy medicines.

The pancreas’ evolved response to injury or infection, the activation of these pancreatic stellate cells is useful in walling off bacteria or dying tissue and limiting its damage. But when these cells build a wall around a tumour, they provide it everything it needs to grow as well as protect it from immune cells or chemotherapy medicine.

Researchers have long believed that vitamin D might be the key to inactivating the pancreas’ stellate cells, but previous efforts have failed because even a diseased pancreas was highly effective at breaking down this fat-soluble vitamin. Evans’ team was convinced that vitamin D indeed held the key to reprogramming the environment that sustained pancreatic tumours; they just had to find an analog of the vitamin that could not be dismantled by the pancreas.

Calcipotriol was that variant.

Evans said his team is hopeful that the unique approach to cancer-fighting that is at the heart of the latest research — to genetically reprogram the microenvironment within which tumour cells grow unchecked — will be useful in a wide range of cancers. — By Melissa Healy/Los Angeles Times/MCT

Study tests drug-free therapy for depression in childhood

While every toddler has tantrums and mood swings, some have more serious mental health problems, including depression and anxiety. Researchers at Washington University are now enrolling preschoolers and young children in a study of therapy designed to treat depression without drugs.

The university’s Early Emotional Development Programme hopes to recruit 250 children ages 3 to 7 for the free study.

The children must meet criteria for depression through assessments — they are socially withdrawn, disengaged, fatigued and unable to shake feelings of guilt. The children may have problems with sleep and appetite and are usually not enthusiastic about play time. Eligible children must not have a diagnosis of autism or take any medications for mood disorders.

The treatment, called parent-child interaction therapy and emotion development, involves 18 weeks of one to two-hour sessions in three parts. In each phase, the parent and child are together in a room while a therapist watches through one-way glass, sending directions to the parent’s earpiece.

One of the parents (the researchers requested anonymity for participants because the study is ongoing) said her 4-year-old daughter has reduced her defiant behaviours from 75% of the time to 25% since starting the therapy in May.

“It took our life from being very, very difficult, where everything you do is a struggle, to suddenly now your child is able to brush their teeth,” the mother said. “I was constantly searching for the better way to do things. Now I don’t have to do that because I know this works.”

The first six sessions focus on child-directed interaction. The parent is coached to follow the child’s lead as they play and give lots of praise and positive feedback. So if the child colours, the parent colours too while giving a running commentary — “you’re colouring the sun with a yellow crayon, now you’re stacking the blue blocks.”

The focus is “to let the child know that the parent is paying attention and really approves of the child’s play,” said staff therapist Mary Grace Portell.

In the next phase, the activity is led by the parent, who gives the child specific commands to set expectations. The child is told to sit in the chair or clean up the toys, for example. Parents are coached on fair, consistent and structured discipline.

For the last six weeks, the sessions are focused on emotional development and symptoms of depression. The children learn how to regulate their emotions with help from the parents. They learn kid-friendly relaxation and breathing techniques.

Some of the exercises in the last phase are designed to provoke frustration, anger or guilt in the child. They’ll get a see-through lock box with an attractive toy in it, but the key won’t work. Or during a tea party, the child’s cup is rigged to break.

Parents are taught to physically connect with the child by getting down to their level and putting a hand on their back. They validate the child’s feelings but don’t try to fix the situation right away. Eventually, the right key or a new cup is offered. Other tasks are aimed at helping the child sustain joyful emotions, such as a bubble machine.

In the study’s first year, 35 children are expected to complete the therapy and receive evaluations four months later. So far, parents have reported fewer tantrums and decreased irritability. And the children are better able to express their feelings, Portell said.

“We are seeing dramatic declines in problematic behaviour,” said Dr Joan Luby, who directs the study. “Every single kid is improving.” — By Blythe Bernhard/St Louis Post-Dispatch/MCT