Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017, Monash University
Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia

Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance to targeted therapies.

Dr Luciano Martelotto, from the Monash University Faculty of Medicine, and his collaborators Dr Piro Lito and Yaohua Xue (MSKCC), have performed intricate DNA sequencing tests on single cells using genetic models of and melanoma.

Lung and melanoma are amongst the hardest to treat of the cancers because of their capacity to alter their genetics, developing resistance to targeted therapies. In a paper published today (TBC) in Nature Medicine, the researchers used animal models from tumours derived from patients and single-cell genomics to develop a hypothetical of resistance, called "fitness threshold model," that explains why and how resistance to occurs in these cancers, and identified types of therapies to prevent this process from occurring.

Lead author Dr Martelotto said that until now, the way that these tumours respond and become resistant to targeted therapies has been poorly understood.

"For the first time, we've demonstrated that solid tumours like melanoma and lung cancers can grow back shortly after therapy, but when they do they are made of genetically diverse sub-groups of malignant cells—and, scarily enough, all of these are resistant to treatment. This genetic diversity is what allows the cancers to adapt to the treatment and resist it." Dr Martelotto explains.

The research team's fitness threshold model links the effect of a given drug with the selection of resistance-causing alterations in DNA, resulting in significant implications for the treatment of cancer patients.

Dr Martelotto said that these findings are important for oncologists and patients because they show that the way that drugs are administered during therapy can have a critical impact on the outcome of the response to treatment.

"In our work, we showed that intermittent administration enables simultaneous delivery of multiple targeted therapies while maintaining lower toxicity, and our fitness threshold model explains how other resistance-causing alterations may develop during targeted therapy," Dr Martelotto said.

This important finding sheds light on the development of new therapeutic designs to more effectively treat patients.

Explore further: Clinical trial looks at targeted genetic therapies for lung cancer

More information: Yaohua Xue et al. An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer, Nature Medicine (2017). DOI: 10.1038/nm.4369

Related Stories

Clinical trial looks at targeted genetic therapies for lung cancer

March 21, 2017
Researchers at the University of Cincinnati (UC) College of Medicine are enrolling patients in a clinical trial looking at targeted gene therapies in patients with early stage lung cancer who have had surgery.

Study identifies how cancer cells may develop resistance to FGFR inhibitors

March 2, 2017
A new study by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) has identified a mechanism by which cancer cells ...

Anti-aging gene identified as a promising therapeutic target for older melanoma patients

February 23, 2017
Scientists at The Wistar Institute have shown that an anti-diabetic drug can inhibit the growth of melanoma in older patients by activating an anti-aging gene that in turn inhibits a protein involved in metastatic progression ...

Researchers develop new way to combat drug resistance for melanoma patients

June 30, 2014
Moffitt Cancer Center researchers developed a new way to identify possible therapeutic targets for patients with drug resistant melanoma. It involves using liquid chromatography-multiple reaction monitoring mass spectrometry ...

Researchers discover mechanism leading to drug resistance, metastasis in melanoma

January 12, 2015
Moffitt Cancer Center researchers have discovered a mechanism that leads to resistance to targeted therapy in melanoma patients and are investigating strategies to counteract it. Targeted biological therapy can reduce toxicity ...

Researchers' discovery is milestone in understanding treatment-resistant melanoma

September 11, 2015
Within the past few years, new treatments have begun to turn the tide against metastatic melanoma, improving and even saving the lives of countless people with this deadly disease.

Recommended for you

New drugs are improving survival times for patients with aggressive type of blood cancer, study finds

June 25, 2018
Survival times for a highly aggressive type of blood cancer have nearly doubled over the last decade due to the introduction of new targeted drugs, a Yorkshire study has shown.

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.

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 ...

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 ...

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.