Although lung cancer is the fifth most commonly diagnosed cancer in Australia, it is the leading cause of cancer death. With a five-year survival rate of only 17 percent, the disease has a devastating impact on society. That’s the reason that researchers at the Garvan Institute of Medical Research are focused on finding better ways to target treatment and improve outcomes for patients.
Dr Venessa Chin, medical oncologist at St Vincent’s Hospital and cancer researcher at Garvan, is taking a different approach to looking at whether we can better predict which patients with advanced lung cancer would respond to immunotherapy, using a unique methodology and set of tumour specimens. Dr Chin is using single cell sequencing to examine advanced lung cancer tumours cell by cell, aiming to determine the most effective treatment courses for patients with lung cancer.
Immunotherapy: a new treatment
Over the past three years, immunotherapy – antibody therapy that stimulates the body’s immune system to fight cancer – has been shown to significantly improve outcomes for patients in many cancers.
Now, it is routinely given to people with advanced or incurable lung cancer either as a standalone treatment or in combination with other treatments. However, only half all of patients that receive immunotherapy, which costs thousands of dollars a dose, respond to treatment. Dr Chin, in partnership with the Garvan-Weizmann Centre for Cellular Genomics, is using cellular genomics to identify a ‘marker’ for patients with advanced lung cancer to help tailor therapies. Ultimately, her aim is to track how and why immunotherapies are working for some people with lung cancer and not others.
“Cellular genomics is very cutting-edge technology that allows us to analyse cells on an individual level and tells us information about all the types of cells inside the tumour,” says Dr Chin. “Immunotherapy activates the immune system by turning T-cells on, but for some patients, this activation doesn’t happen. By comparing this activation or inactivation between patients using single cell sequencing, it will allow us to better define the immune landscape of patients with advanced lung cancer and from this, better predict those patients who are going to benefit from immunotherapy.”
A unique approach
The majority of published molecular profiling work on lung cancer has used specimens from surgically curable patients, meaning that patients with advanced or metastatic disease, which makes up the majority of diagnoses, are grossly underrepresented.
“In our lab, we collect specimens from patients with advanced or metastatic lung cancer, which is quite unique,” says Dr Chin.
“The way in which we collect the specimens also gives us an advantage. By using a method in which the cells can be gently mechanically disassociated into a single cell suspension as opposed to chemically digesting the tissue, we remove the risk of affecting protein expression in the cell.
"We want to use these specimens and the spectrum of immune cells contained in them to determine why immunotherapy works for some people and not others.”
An evolving challenge
As a medical oncologist, Dr Chin understands firsthand the difficulty that clinicians face when treating patients with lung cancer.
“When you’re in the clinic trying to treat a patient with lung cancer, it’s incredibly difficult to know whether treatment ‘a’ will be better than ‘b’ or ‘c’. As a clinician I want to ensure that my patients receive the best possible treatment right from the outset. It’s critical for clinicians to try and make those decisions in as informed a way as possible,” says Dr Chin.
“Immunotherapy as a treatment is really interesting,” says Dr Chin.
“The success of these drugs has far outstripped our understanding of why and how they work. Now as they’re becoming more common as a treatment for not only lung cancer but kidney, bladder and melanoma cancer as well, funding them is going to become an issue for the Pharmaceutical Benefits Scheme, so studies like this are going to become increasingly necessary.”
Although the study is in its early stages, Dr Chin is hoping to categorise patients into broad groups, based on whether they are highly likely to respond to immunotherapy, highly unlikely to respond to immunotherapy or may respond to it when used in a combination approach with adjunctive therapies.
The project is well underway, with a range of samples being collected and some preliminary results expected by February. “It will really give us an idea of what the spectrum is and what the heterogeneity is between patients,” says Dr Chin.
“I think this year will be telling about where we go with the project. Depending on funding, I think we’ll be able to complete some significant the single cell sequencing and additional analysis.”