Researchers Make a Breakthrough Concerning Treatment-Resistant Cancers

Scientists 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 become resistant to targeted therapies.

Cancers Developing Resistance to Treatments

Fitness Threshold Model

Lung cancer and melanoma are some of the most difficult cancers to treat because of their ability to alter their genetics and resist targeted therapies. A paper published in Nature Medicine reported that researchers used animal models from tumors taken from patients and single-cell genomics to develop a theory of resistance, called a “fitness threshold model.” This model explained how and why therapy resistance occurs in these cancers, as well as identified different therapies that can be used to prevent this process from happening.

How Cancers Grow Back

Researchers have showed that solid tumors like melanoma and certain lung cancers are able to grow back shortly after therapy. However, when these tumors do grow back, they are made of genetically diverse sub-groups of malignant cells. As they grow back, the cells are all mutated enough to be treatment resistant. This genetic diversity explains how the cancers can adapt to resist the treatment.


The fitness threshold model links the effectiveness of a drug with the different resistance-causing alterations in DNA. These findings help oncologists understand how and why drugs that are administered during therapy can have a critical impact on the response to treatment.

Varied drug administration simultaneously delivers various targeted therapies while maintaining a lower toxicity level. The fitness threshold model explains how other resistance-causing genetic alternations may develop during targeted therapy. Scientists are now able to develop new therapeutic drugs to treat patients more effectively in the future.

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