New study proves one lung cancer subtype can switch to another

April 14, 2017 by Allison Perry, University of Kentucky
Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia

A new study co-authored by a researcher starting her laboratory at the University of Kentucky Markey Cancer Center shows that in certain genetic situations, one non-small cell lung cancer subtype can change into another subtype.

This 'lineage switching' could underlie resistance to therapeutics, and this research examines exactly how the lineage switch can happen. The work was a collaborative effort between laboratories in Kentucky, New York and Boston.

Previously, it was unclear which in the adult can be the 'cells-of-origin' of the two major subtypes of non-small cell lung , namely and . Likewise, it was unclear what differences in DNA organization define the two distinct lung cancer subtypes. The existence of adenosquamous lung tumors, clinically defined by the presence of both glandular adenocarcinoma lesions and fully stratified squamous lesions within the same tumor, suggested that both adenocarcinomas and squamous cell carcinomas could come from the same cells in the lung, but clear evidence for this theory was lacking.

Published in Nature Communications, the study showed that adenocarcinoma cells can change to squamous cells due to reorganization of their DNA in specific ways. Beginning with a mouse model of adenosquamous lung tumors, researchers validated the genetics by comparing it to human adenosquamous lung tumor – the genetics are often the same, including activation of the oncogene KRAS and the deletion of the suppressor Lkb1. The team then used transplant assays to demonstrate that established adenocarcinoma tumors could transition to squamous cell carcinomas in the mouse lung.

Lastly, the group isolated different lung cells, and demonstrated that only certain lung cells could give rise to tumors capable of undergoing the lineage switch.

"This data is exciting because it shows which cells in the lung can give rise to adenosquamous tumors," said study co-author Christine Fillmore Brainson, assistant professor in the UK department of toxicology and cancer biology. "And the technique we used to transform the isolated cells can be applied to many lung cancer models."

Oncologists have observed this 'lineage switching' after the failure of EGFR tyrosine kinase inhibitor treatment, when it is clinically justifiable to take a second biopsy. However, second biopsies are not normally done after chemotherapy, a practice that Brainson thinks could be revised to understand the exact mechanisms of therapy resistance.

"Now that we have a glimpse into the molecular mechanism of lineage switching, we can begin to learn how to manipulate this phenomenon for better therapeutic outcomes," said Brainson.

Explore further: Researchers identify mechanism of oncogene action in lung cancer

More information: Haikuo Zhang et al. Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2, Nature Communications (2017). DOI: 10.1038/ncomms14922

Related Stories

Researchers identify mechanism of oncogene action in lung cancer

January 19, 2017
Researchers at Mayo Clinic have identified a genetic promoter of cancer that drives a major form of lung cancer. In a new paper published this week in Cancer Cell, Mayo Clinic researchers provide genetic evidence that Ect2 ...

Drug combination shuts down cancer stem cells and tumor growth in aggressive lung cancer

March 14, 2016
Researchers on Mayo Clinic's Florida campus have shut down one of the most common and lethal forms of lung cancer by combining the rheumatoid arthritis drug auranofin with an experimental targeted agent.

Researchers discover an inactive tumor suppressor gene in lung cancer

April 14, 2015
Researchers at Genes and Cancer group at Bellvitge Biomedical Research Institute (IDIBELL), led by Montse Sanchez-Cespedes, have identified the PARD3 gene as a tumor suppressor that is inactivated in lung cancer squamous ...

Lung cancer metastases may travel through airways to adjacent or distant lung tissue

December 30, 2014
A new study by researchers in Canada supports the hypothesis that lung cancer, particularly adenocarcinoma, may spread through the airways. The putative occurrence of intrapulmonary aerogenous metastasis of lung cancer has ...

Researchers inhibit tumor growth in new subtype of lung cancer

August 3, 2016
Lung cancer is the most common cause of cancer deaths, accounting for about a third of all tumor-related deaths. Adenocarcinomas, a non-small cell lung cancer (NSCLC), account for about 40 percent of cancer diagnoses, but ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.