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Potential therapy for drug-defying gallbladder cancer

Geneticists have discovered genetic mutations that make for promising targets for developing novel therapies for gallbladder cancer1.

Gallbladder cancer severely affects the liver, gallbladder and bile duct. Chemotherapy and other palliative treatments cannot significantly increase the survival rate of gallbladder cancer patients.

In search of new therapies for gallbladder cancer, scientists from the Advanced Centre for Treatment Research Education in Cancer (ACTREC), at the Tata Memorial Centre in Mumbai, India, sequenced the genes of early-stage tumour cells isolated from gallbladder cancer patients.

The team, led by Amit Dutt, identified novel mutations in specific modifier genes that are known to play a significant role in other types of cancers.

Of all the mutations, mutations in the ERBB2 gene showed an overall frequency of 13 per cent in six of 44 gallbladder cancer patients.

The genetic mutation they found in ERBB2 encodes a protein that activates a signalling pathway by binding to epidermal growth factor receptor (EGFR), a cell-surface protein.

The researchers then used a small inhibitor molecule that disrupted the activities of ERBB2 and EGFR. This, in turn, diminished the survival, migration and invasion of gallbladder cancer cells, suggesting its potential as a drug target.

The researchers also identified an additional genetic mutation (KRAS) that is thought to prevent gallbladder cancer patients from responding to cancer therapies.

This genetic mutation could act as a new drug target to combat drug-defying gallbladder cancer, says Dutt.



  1. Iyer, P. et al. ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer. Int. J. Canc. (2018) doi: 10.1002/ijc.31916

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