Navigation Links
Study identifies pathway to enhance usefulness of EGFR inhibitors in lung cancer treatment

Many lung cancers are driven by mutations in the epidermal growth-factor receptor (EGFR), and so it makes sense that many successful modern treatments block EGFR activity. Unfortunately, cancers inevitably evolve around EGFR inhibition, and patients with lung cancers eventually relapse. A University of Colorado Cancer Center study published today in the journal Cancer Research details a signaling pathway, known as 'the canonical Wnt pathway', that lung cancer cells use to escape from EGFR-targeted therapy and suggests that by disrupting this pathway, we could lengthen the usefulness of existing EGFR inhibition therapies.

"As Billy Crystal as Miracle Max said in The Princess Bride, 'There's a big difference between mostly dead and all dead,' and in lung cancer cells, the Wnt pathway could be that difference," says James DeGregori, PhD, investigator at the CU Cancer Center, co-director of the center's Molecular Oncology Program, and the paper's senior author.

Elaborating on DeGregori's very technical description, Matias Cass-Selves, PhD, postdoc in the DeGregori lab and the paper's first author, explains, "The Wnt pathway is an ancient mechanism across species that helps stem cells differentiate into tissue, and maintains stem cells' ability to stay 'stemmy' to produce subsequent generations of cells that can also continue to produce cells. It also maintains adult lung tissue, and now we've shown that it also maintains cancer cells during targeted therapy."

Imagine a dish filled with millions of lung cancer cells. And imagine the cells' genetic material as a shared book. Cass-Selves systematically deleted paragraphs from cells' books to create a population of cells, each with a unique paragraph deleted. Then he treated all the cells with an EGFR inhibitor. Which cells died? Well, a number of paragraphs were responsible for cell death, "But many of the paragraphs missing from the dead cells were within the Wnt chapter," he says.

Break the flow of this Wnt chapter, and you break the ability of cells to withstand EGFR inhibition therapy. EGFR inhibitors currently employed in the clinic include popular drugs like gefitinib, erlotinib and cetuximab. Combining EGFR inhibitors with a hypothetical Wnt inhibitor could make the effects of these useful drugs more durable.

It turns out this Wnt inhibitor may be more than hypothetical.

"Traditionally, the Wnt pathway has been considered to be a hard pathway to drug, since there are not many easily druggable enzymes in it, but we were lucky in that just as we were finding roles for Wnt in lung cancer cell survival, other research teams discovered that a group of enzymes, called tankyrases, are key for the correct functioning of Wnt. Not only that, these groups also designed tankyrase inhibitors which were available for all researchers," Cass-Selves says.

And so instead of what could have been a lengthy search for a drug, the idea of Wnt inhibition combined with EGFR inhibition goes straight into the preclinical pipeline.


Contact: Garth Sundem
University of Colorado Denver

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. Law that regulates shark fishery is too liberal: UBC study
3. New study will help protect vulnerable birds from impacts of climate change
4. Study jointly led by UCSB researcher supports theory of extraterrestrial impact
5. BYU study: Using a gun in bear encounters doesnt make you safer
6. 15-year study: When it comes to creating wetlands, Mother Nature is in charge
7. Pycnogenol (French maritime pine bark extract) shown to improve menopause symptoms in new study
8. Crystal structure of archael chromatin clarified in new study
9. EU-funded study underlines importance of Congo Basin for global climate and biodiversity
10. University of Houston study shows BP oil spill hurt marshes, but recovery possible
11. Study demonstrates cells can acquire new functions through transcriptional regulatory network
Post Your Comments:
(Date:4/15/2016)... DUBLIN , April 15, 2016 ... of the,  "Global Gait Biometrics Market 2016-2020,"  report ... ) , ,The global gait ... CAGR of 13.98% during the period 2016-2020. ... movement angles, which can be used to compute ...
(Date:4/13/2016)... 2016  IMPOWER physicians supporting Medicaid patients in ... clinical standard in telehealth thanks to a new partnership ... platform, IMPOWER patients can routinely track key health measurements, ... index, and, when they opt in, share them with ... a local retail location at no cost. By leveraging ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 On Wednesday, June ... 4,833.32, down 0.22%; the Dow Jones Industrial Average edged 0.27% ... at 2,085.45, down 0.17%. has initiated coverage on the ... Nektar Therapeutics (NASDAQ: NKTR ), Aralez Pharmaceuticals Inc. ... BIND ). Learn more about these stocks by ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance ... consulting, provides a free webinar on Performing Quality Investigations: Getting to ... 12pm CT at no charge. , Incomplete investigations are still a major concern ...
(Date:6/23/2016)... FRANCISCO , June 22, 2016  Amgen (NASDAQ: ... sponsorship of the QB3@953 life sciences incubator ... human health. The shared laboratory space at QB3@953 was ... overcome a key obstacle for many early stage organizations ... part of the sponsorship, Amgen launched two "Amgen Golden ...
(Date:6/22/2016)... DIEGO , June 22, 2016 ... that will allow them to produce up to ... from one lot within one week. These high-quality, ... time laboriously preparing cells and spend more time ... possible through a proprietary, high-volume manufacturing process that ...
Breaking Biology Technology: