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 Casás-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. Casás-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," Casás-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.
Journal reference: Cancer Research
Provided by University of Colorado Denver
- Research reveals what drives lung cancer's spread Jul 02, 2009 | not rated yet | 0
- The right combination: Overcoming drug resistance in cancer Jun 01, 2012 | not rated yet | 0
- EGFR protects cancer cells from starvation via a kinase-independent mechanism May 05, 2008 | not rated yet | 0
- New study helps predict which lung cancer drugs are most likely to work Jan 10, 2012 | not rated yet | 0
- EGFR gene signature predicts non-small cell lung cancer prognosis Jan 13, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer 7 hours ago | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer 7 hours ago | not rated yet | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer 10 hours ago | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer 11 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer 11 hours ago | 5 / 5 (3) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
5 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
10 hours ago | 5 / 5 (3) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
7 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
8 hours ago | 5 / 5 (2) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
4 hours ago | not rated yet | 0
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
5 hours ago | not rated yet | 0