CR3 News Magazine 2019: November Issue - WHY Only $14 Million? - Page 35

“Initially, it was shocking, devastating,” she said. “But we (along with her husband Brian) also knew we couldn’t wallow in our sadness. We had a 3 ½-year-old girl (Paige) and a baby on the way, so we were going to fight for our kids.”

Emily stayed in the hospital and delivered her baby, Brady, but her diagnosis precluded the new-mother things, like nursing and a quick release from the hospital, she enjoyed with Paige. What should have been a celebratory time felt overshadowed by a startling and grim diagnosis.

She remembers the trip home from the hospital with Brian – Paige was at home with Emily’s parents – where “we pulled over on the side of the road and broke down.”

Pivotal decision for personalized care

Brian Daniels, a former football standout at

the University of Colorado, consulted a handful orthopedic doctors he knew from his playing days. Their advice: Get an appointment with Ross Camidge, MD, PhD, professor and director of thoracic oncology, at the CU Anschutz Medical Campus. “He’s one of the best in the world with this targeted therapy,” Emily said. “It was a no-brainer … this is where I needed to do my treatment.”

The decision has proven to be pivotal, as Camidge, in collaboration with Robert Doebele, MD, PhD, associate professor of medicine, CU School of Medicine, eventually devised a completely novel and personalized treatment that has, for more than eight months, stopped the spread of Emily’s cancer.

However, before making this major discovery, which will be presented at next week’s World Conference on Lung Cancer in Barcelona, Emily’s medical team worked through their clinical bag of tricks in a very short time. In the ensuing battle, it was readily apparent that Emily’s cancer did not play by the normal rules.

Targeted therapies

In basic terms, the cancer battle comes down to exposure and attack: identifying the genetic pathways that enable cancer to grow, and developing therapies that inhibit those pathways.

Soon after Emily was first seen in the lung cancer multi-disciplinary clinic at the CU Cancer Center Camidge quickly discovered that she had ALK-positive non-small cell lung cancer. Over a decade ago, Camidge was on the clinical-trial forefront that developed the first treatment for lung cancers driven by acquired changes in the anaplastic lymphoma kinase (ALK) gene, causing the cells to grow abnormally fast and aggressively.

A few years later, the initial drug was replaced by more effective ones; Camidge co-led an international trial in 2017 that established alectinib as the initial go-to therapy for this sub-type of lung cancer.

In late-February 2018, Emily started on alectinib and initially responded well to the four pills taken in the morning and four more in the evening. But in just a couple months, her cancer was progressing again.

Another biopsy, tested with the CU Colorado Molecular Correlates Laboratory’s cutting-edge assays, did not show any identifiable reason for the cancer’s resistance. Camidge tried another ALK inhibitor, brigatinib – a drug he also helped develop and one that showed great promise for longer-duration disease control.

However, within a month, Emily’s cancer was progressing again.

Living cells are key to breakthrough

In June 2018, the addition of a specific chemotherapy regimen, identified by Camidge in 2011 as being particularly effective in ALK-positive lung cancer, helped stop her cancer – but only for 3 ½ months. The team then applied another CU-developed treatment strategy: weeding the garden – or radiotherapy treatment of “oligo-progression” as Camidge’s team coined it – whereby they kept Emily on her drug treatments while treating individual spots of cancer with highly focused radiation.

However, nothing completely slowed the cancer. “My colleague Dr. Bob Doebele had this idea that not everything driving resistance in a cancer cell can be found just by looking with the already-established tests,” Camidge said.

Doebele knew there were only a certain number of interrogations that could be done on the kind of preserved pieces of tissue from biopsies like the one sent to the Colorado Molecular Correlates lab. So when the biopsy of Emily’s cancer was taken, as part of a CU research protocol, some of her cancer was sent directly to Doebele’s lab to see if live cancer cells could be grown from it.

“When Bob grows it and it’s living, he can poke it and see which signaling pathways go up and down,” Camidge said. “He was able to deduce that Emily’s cancer had become dependent on another signaling pathway, separate from the ALK side of things.”

That pathway is called MET, and it essentially acts as a second driver of Emily’s cancer.

‘Responded like a dream’

Importantly, all of the known ways of activating MET, the methods doctors test for it in preserved cancer tissue, showed normal results. The key difference were the living cells.

Dr. Ross Camidge

BREAKTHROUGH ON WORLD STAGE

Camidge and Doebele are co-authors on the report about the living-cell line that gave doctors insight into Emily Daniels’ cancer and resulted in her novel, personalized treatment regimen that will be presented at the World Conference on Lung Cancer in early September.

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