Double-drug strategy blocks escape route for most lung cancers

April 3, 2018 by Cathy Frisinger, UT Southwestern Medical Center
A new study demonstrated that using two currently available drugs could be an effective treatment for the majority of lung cancers. The bottom row shows tumors treated with the drug combo, compared with tumors without treatment or with single treatments in the rows above. Credit: UT Southwestern

A one-two combo punch using two currently available drugs could be an effective treatment for the majority of lung cancers, a study by scientists with UT Southwestern's Simmons Cancer Center shows.

Researchers found that a combination of drugs - one targeting epidermal growth factor receptor (EGFR) and one targeting tumor necrosis factor (TNF) - effectively blocks the cancer from using TNF as an escape route. Using a mouse model, the researchers showed that when TNF is also blocked, the cancer becomes sensitive to EGFR treatment.

"There has been a tremendous effort over the past several years to block EGFR as a treatment for , but this therapy only works in a small subset of patients. The cancer fights back with a bypass pathway," said senior author Dr. Amyn Habib with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and a staff physician at the Dallas Veterans Affairs Medical Center.

"Blocking both of these proteins could be a treatment that is beneficial for the majority of cancer patients," said Dr. Habib, Associate Professor of Neurology and Neurotherapeutics with UT Southwestern's Peter O'Donnell Jr. Brain Institute.

Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute and in 2017, lung cancer caused 26 percent of all cancer deaths. Non-small cell lung cancer (NSCLC), the type of lung cancer for which the EGFR/TNF inhibitor combination would be effective, comprises approximately 85 percent of all lung cancers.

The latest findings build on previous work by Dr. Habib's lab showing that the same combination of drugs was successful in a mouse model of glioblastoma, a deadly type of brain cancer.

Researchers are now planning a phase 2 clinical trial of the two-drug strategy, and because the two drugs are already FDA-approved, they hope to be able to launch the trial within a year, said oncologist Dr. David Gerber with the Simmons Cancer Center, who will lead the trial.

The clinical trial being planned will test the treatment in both and those with glioblastomas.

"If this strategy is effective, then it might be broadly applicable not only against lung cancer but also against other cancers that express EGFR, which include brain, colon, and head and neck cancers," said Dr. Gerber, Associate Professor of Internal Medicine and Clinical Sciences.

Another advantage of the anti-EGFR/TNF strategy is that the drugs are well-tolerated. Both the EGFR inhibitors and TNF inhibitors fall into the category of targeted drugs, meaning they affect specific molecules within cancer cells, and therefore have fewer side effects. Traditional chemotherapy drugs, on the other hand, have broad effects, killing cells in both cancer and healthy tissue, and leading to many unpleasant side effects.

Until now, EGFR inhibitors have only been effective at treating the 10 to 15 percent of non-small cell lung cancers that have a variant of EGFR, but the two-drug combo could potentially work for all non-small cell lung cancers, explained Dr. John Minna, Director of the Hamon Center for Therapeutic Oncology Research and Professor of Internal Medicine and Pharmacology.

"This finding has the possibility of dramatically altering how we treat lung ," said Dr. John Minna, who holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology at UT Southwestern, which is recognizing its 75th-year anniversary in 2018.

The research appears in the Journal of Clinical Investigation.

Other UT Southwestern faculty members who contributed to this research are: Dr. Boning Gao, Assistant Professor with the Hamon Center for Therapeutic Oncology Research and Pharmacology; Dr. Kimmo Hatanpaa, Associate Professor of Pathology; Dr. Kemp Kernstine, Professor of Cardiovascular and Thoracic Surgery and holder of the Robert Tucker Hayes Foundation Distinguished Chair in Cardiothoracic Surgery; Dr. Yang Xie, Associate Professor of Clinical Sciences and Bioinformatics; Dr. Hong Zhu, Assistant Professor of Clinical Sciences and with the Simmons Cancer Center; Dr. Farjana Fattah, Assistant Professor with the Simmons Cancer Center and Pathology; Dr. Masaya Takahashi, Associate Professor with the Advanced Imaging Research and Radiology; Dr. Bipasha Mukherjee, Assistant Professor of Radiation Oncology; Dr. Sandeep Burma, Associate Professor of Radiation Oncology; and Dr. Jonathan Dowell, Professor of Internal Medicine.

Explore further: Researchers demonstrate RAS dimers are essential for cancer

More information: Ke Gong et al, TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI96148

Related Stories

Researchers demonstrate RAS dimers are essential for cancer

January 11, 2018
Mutated RAS genes are some of the most common genetic drivers of cancer, especially in aggressive cancers like pancreatic and lung cancer, but no medicines that target RAS are available despite decades of effort.

The silencer: Study reveals how a cancer gene promotes tumor growth

June 23, 2016
A Yale-led study describes how a known cancer gene, EGFR, silences genes that typically suppress tumors. The finding, published in Cell Reports, may lead to the development of more effective, individualized treatment for ...

New therapeutic targets for small cell lung cancer identified

July 21, 2016
UT Southwestern Medical Center researchers have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer and that, when deleted in the lungs of mice, prevents the cancer from forming.

Study finds breast cancer driver, HER2, in 3 percent of lung cancers

July 27, 2017
The Lung Cancer Mutation Consortium at the University of Colorado Cancer Center reports this week in the journal Cancer that 24 of 920 patients (3 percent) with advanced-stage lung cancer had mutations in the gene HER2. Seventy-one ...

Scientists reveal that new combination of clinically tested drugs inhibits growth of lung tumors

September 8, 2017
Research at the University of Southern Denmark has revealed that a new combination of clinically tested drugs inhibits the growth of tumours, thereby potentially improving patients' survival.

Lung cancer patients gain access to new treatment for fourth time in two months

December 2, 2015
The International Association for the Study of Lung Cancer (IASLC) is pleased to hear of another approval by the U.S. Food and Drug Administration (FDA) that helps in the fight against lung cancer—the fourth in two months. ...

Recommended for you

Magnetized wire could be used to detect cancer in people, scientists report

July 16, 2018
A magnetic wire used to snag scarce and hard-to-capture tumor cells could prove to be a swift and effective tactic for early cancer detection, according to a study by researchers at the Stanford University School of Medicine.

Researchers suggest new treatment for rare inherited cancers

July 16, 2018
Studying two rare inherited cancer syndromes, Yale Cancer Center (YCC) scientists have found the cancers are driven by a breakdown in how cells repair their DNA. The discovery, published today in Nature Genetics, suggests ...

Researchers map 'family trees' of acute myeloid leukemia

July 16, 2018
For the first time, a team of international researchers has mapped the family trees of cancer cells in acute myeloid leukaemia (AML) to understand how this blood cancer responds to a new drug, enasidenib. The work also explains ...

Looking at the urine and blood may be best in diagnosing myeloma

July 13, 2018
When it comes to diagnosing a condition in which the plasma cells that normally make antibodies to protect us instead become cancerous, it may be better to look at the urine as well as the serum of our blood for answers, ...

Massive genome havoc in breast cancer is revealed

July 12, 2018
In cancer cells, genetic errors wreak havoc. Misspelled genes, as well as structural variations—larger-scale rearrangements of DNA that can encompass large chunks of chromosomes—disturb carefully balanced mechanisms that ...

Study shows biomarker panel boosts lung cancer risk assessment for smokers

July 12, 2018
A four-protein biomarker blood test improves lung cancer risk assessment over existing guidelines that rely solely upon smoking history, capturing risk for people who have ever smoked, not only for heavy smokers, an international ...

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.