Drug Resistant Melanoma Caused Due to Break in Genes!



Drug Resistant Melanoma Caused Due to Break in Genes!

Melanoma is an extremely fatal form of skin cancer and has inherent resistance to both radiotherapy and chemotherapy (1 Trusted Source
Chemotherapy Resistance Mechanisms in Advanced Skin Cancer

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The occurrence of Melanoma has been increasing steadily and become a major health issue since the 5-year survival rate has reduced to less than 5%. This is due to the resistance of melanoma to chemotherapeutic agents either due to changes in enzyme systems, defective transport systems, or damage due to the chemotherapeutic drug.

Clinical Studies on the Cause of Drug Resistance of Melanomas

In various studies, it was found that mutation of the BRAF gene occurs in approximately 1 in 2 cases with Melanoma. This gene usually produces the protein that helps regulate cell growth. Mutation of this gene can cause cells to grow uncontrollably and lead to the development of cancer. These studies led to the development of targeted therapies to simultaneously target BRAF mutations and MEK, another gene. However, within one year, these therapies also showed relapse in 50% of patients.

In a recent study published in the journal Cell Reports the mechanism of developing resistance to targeted therapy has been reported. The reports indicated that melanomas have the ability to ‘break’ certain segments of the BRAF gene, referred to as genomic deletions, in response to the treatment. This leads to the tumor creating alternative versions of the protein (altBRAFs) This, in turn, reduces the effectiveness of the drugs.

The researchers also discovered that the same genetic deletions occurred in untreated melanomas, suggesting the melanomas can develop drug resistance on their own, without being exposed to any drugs.

Combating Cancer-Future treatments

Dr. Francisco Aya Moreno, a medically-trained oncologist and recent PhD graduate at the Centre for Genomic Regulation (CRG) in Barcelona explained “There is an emerging class of drugs known as second-generation RAF inhibitors. Unlike BRAF inhibitors, these drugs have a broad spectrum, and so could potentially inhibit the function of altBRAFs. Clinical trials that are assessing their effectiveness should also expand to include melanoma patients with a normal functioning BRAF gene as well, and possibly to other cancer types which express altBRAFs,”

Dr. Aya Moreno concluded stating that the study helped understand how melanomas rest treatment and how this data would help in developing effective therapies for patients. He further added that a combination of clinical expertise and scientific research is important in moving forward in the fight against cancer.



  1. Chemotherapy Resistance Mechanisms in Advanced Skin Cancer – (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379221/)



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