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AUGUST 2017 | Published by RCPA

Issue #072

Lung cancer is becoming a bigger target for molecular pathologists

Lung cancer is becoming a bigger target for molecular pathologists

The stats for lung cancer are bleak. It is the leading cause of all cancer deaths in Australia and New Zealand, and the chance of surviving this disease for five years is just 16%. However, advances in lung cancer genomics have given pathologists new targets to attack, and they are taking aim with increasing accuracy to both diagnose and guide treatment of subsets of this disease.

Associate Professor Wendy Cooper, Anatomical and Molecular Pathologist at Royal Prince Alfred Hospital’s Department of Tissue Pathology and Diagnostic Oncology in Sydney, says a proportion of lung adenocarcinomas have changes in a range of genes that are candidates for targeted therapy.

“For example, adenocarcinomas harbouring activating EGFR (epidermal growth factor receptor) gene mutations or anaplastic lymphoma kinase (ALK) or ROS1 gene rearrangements are sensitive to specific types of targeted therapies,” she explains.

Adenocarcinoma is the most common type of lung cancer. It is a cancer of mucous-secreting glands that can occur anywhere in the body, including in the lungs, and is a sub-type of non-small call lung cancer (NSCLC). Other sub-types, such as squamous cell carcinoma, don’t harbour these mutations.

“Targeted therapy works on specific mutations by switching off the protein that the mutation switched on. For example, the EGFR mutation leads to abnormal constant activation of the protein that plays a role in increasing cell production and cellular survival that drives the tumour. Targeted therapy switches this protein off so it can’t cause these effects,” says A/Prof Cooper.

She says all lung adenocarcinomas should be tested to see if they have a targetable mutation.

There is also hope for a broader population of lung cancer patients courtesy of advances in immunotherapy.

“Immunotherapy for lung cancer is hugely promising and the type of patients who are more likely to benefit from this type of treatment is still being worked out,” explains A/Prof Cooper.

The aim of immunotherapy is to overcome the mechanism the tumour uses to dampen the body’s immune response to it. Immunotherapy agents block this mechanism, enabling the patient’s own immune system to fight the cancer.

“It’s not a mutation we are targeting, but we are profiling a tumour and looking for a molecule, which in this case is the protein programmed death-ligand 1(PD-L1). This is a type of protein that plays a major role in supressing the immune system. The immunohistochemical test for this protein is performed on the lung tissue biopsy by an anatomical pathologist.”

The stats on lung cancer are grim, and this is mostly attributed to it being diagnosed when it’s quite advanced. The rise of these new approaches to diagnose, molecularly characterise and treat lung cancer may help to turn these stats around, but only time will tell.

Lung cancer was covered in the February 2013 edition of ePathWay.




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