The anti-cancer drug abemaciclib (also known as Vernezio) has this month been added to the Australian Pharmaceutical Benefits Scheme (PBS) to treat certain types of breast cancer.

This significantly reduces the cost of the drug. A patient can now expect to pay A$31.60 for a 28-day supply ($7.70 with a health care concession card). The price of abemaciclib without government subsidy is $4,250.

So what is abemaciclib, and how did we get to this point?

It stops cells dividing

Researchers at the pharmaceutical company Eli Lilly developed abemaciclib and published the first study on the drug (then known as LY2835219) in 2014.

Abemaciclib is a type of drug known as a “cyclin-dependent kinase inhibitor”. It’s taken as a pill twice a day.

To maintain our health, many of the cells in our bodies need to grow and divide to produce new cells. Cancers develop when cells grow and divide out of control. Therefore, stopping cells from dividing into new cells is one way that cancer can be fought.

When cells divide, they have to make a copy of their DNA to pass onto the new cell. “Cyclin-dependent kinases” (CDKs for short) are essential for this process. So, if you stop the CDKs, you stop the DNA copying, you stop cells dividing, and you fight the cancer.

However, there are different types of CDKs, and not all cancers need them all to grow. Abemaciclib specifically targets CDK4 and CDK6. Thankfully, a lot of cancers do need these CDKs, including some breast cancers.

But abemaciclib will only be effective against cancers that rely on CDK4 and CDK6 for continued growth. This specificity also means abemaciclib is fairly unique, so it can’t easily be replaced with a different drug.

Two other CDK4/6 inhibitors were developed around the same time as abemaciclib, and are called ribociclib and palbociclib. Both of these drugs are also on the PBS for specific types of breast cancer. As the drugs differ in their chemical structures, they have slight differences in the way they are taken up and processed by the body. The preferred drug given to a breast cancer patient will depend on their unique circumstances.

What are the side effects?

Research is still ongoing into the differences between each of these CDK4/6 inhibitors, but it is known that the side effects are largely similar, but can differ in severity.

The most common side effects of abemaciclib are fatigue, diarrhoea and neutropenia (reduced white blood cells). The gastrointestinal issues are generally more severe with abemaciclib.

If these side effects are too severe, abemaciclib treatment can be stopped.

What types of cancer has abemaciclib been approved for?

In 2017, the United States Food and Drug Administration (FDA) approved abemaciclib for the treatment of patients with metastatic HR+/HER2- (hormone receptor-positive and human epidermal growth factor receptor 2-negative) breast cancer who did not respond to standard endocrine therapy.

Australia’s Therapeutic Goods Administration (TGA) similarly approved abemaciclib in 2022 as an “adjuvant” therapy (after the initial surgery to remove the tumour) for patients with HR+/HER2- invasive early breast cancer which had spread to lymph nodes and was at high risk of returning.

As of May 1 2024, the PBS covers this use of abemaciclib in combination with endocrine therapy such as fulvestrant, which is also listed on the PBS. Endocrine therapy, also known as hormonal therapy, blocks hormone receptor positive (HR+) cancers from receiving the hormones they need to survive.

Could abemaciclib be used for other cancers in the future?

Abemaciclib is of great interest to scientists and medical practitioners, and testing is ongoing to assess the effectiveness of abemaciclib in treating a range of other cancers, including gastrointestinal cancers and blood cancers.

Abemaciclib may even be usable in brain cancers, as it has long been known to be capable of crossing the blood-brain barrier, a common stumbling block for potential anti-cancer drugs.

Time will tell whether the role of abemaciclib in health care will be expanded. But for now, its inclusion on the PBS is sure to bring some relief to breast cancer patients nationwide.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute and John (Eddie) La Marca, Senior Resarch Officer, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Over the past several days, the world has watched on in shock as wildfires have devastated large parts of Los Angeles.

Beyond the obvious destruction – to landscapes, homes, businesses and more – fires at this scale have far-reaching effects on communities. A number of these concern human health.

We know fire can harm directly, causing injuries and death. Tragically, the death toll in LA is now at least 24.

But wildfires, or bushfires, can also have indirect consequences for human health. In particular, they can promote the incidence and spread of a range of infections.

Effects on the immune system

Most people appreciate that fires can cause burns and smoke inhalation, both of which can be life-threatening in their own right.

What’s perhaps less well known is that both burns and smoke inhalation can cause acute and chronic changes in the immune system. This can leave those affected vulnerable to infections at the time of the injury, and for years to come.

Burns induce profound changes in the immune system. Some parts go into overdrive, becoming too reactive and leading to hyper-inflammation. In the immediate aftermath of serious burns, this can contribute to sepsis and organ failure.

Other parts of the immune system appear to be suppressed. Our ability to recognise and fight off bugs can be compromised after sustaining burns. Research shows people who have experienced serious burns have an increased risk of influenza, pneumonia and other types of respiratory infections for at least the first five years after injury compared to people who haven’t experienced burns.

Wildfire smoke is a complex mixture containing particulate matter, volatile organic compounds, ozone, toxic gases, and microbes. When people inhale smoke during wildfires, each of these elements can play a role in increasing inflammation in the airways, which can lead to increased susceptibility to respiratory infections and asthma.

Research published after Australia’s Black Summer of 2019–20 found a higher risk of COVID infections in areas of New South Wales where bushfires had occurred weeks earlier.

We need more research to understand the magnitude of these increased risks, how long they persist after exposure, and the mechanisms. But these effects are thought to be due to sustained changes to the immune response.

Microbes travel in smoky air

Another opportunity for infection arises from the fire-induced movement of microbes from niches they usually occupy in soils and plants in natural areas, into densely populated urban areas.

Recent evidence from forest fires in Utah shows microbes, such as bacteria and fungal spores, can be transported in smoke. These microbes are associated with particles from the source, such as burned vegetation and soil.

There are thousands of different species of microbes in smoke, many of which are not common in background, non-smoky air.

Only a small number of studies on this have been published so far, but researchers have shown the majority of microbes in smoke are still alive and remain alive in smoke long enough to colonise the places where they eventually land.

How far specific microbes can be transported remains an open question, but fungi associated with smoke particles have been detected hundreds of miles downwind from wildfires, even weeks after the fire.

So does this cause human infections?

A subset of these airborne microbes are known to cause infections in humans.

Scientists are probing records of human fungal infections in relation to wildfire smoke exposure. In particular, they’re looking at soil-borne infectious agents such as the fungi Coccidioides immitis and Coccidioides posadasii which thrive in dry soils that can be picked up in dust and smoke plumes.

These fungi cause valley fever, a lung infection with symptoms that can resemble the flu, across arid western parts of the United States.

A study of wildland firefighters in California showed high rates of valley fever infections, which spurred occupational health warnings including recommended use of respirators when in endemic regions.

A California-based study of the wider population showed a 20% increase in hospital admissions for valley fever following any amount of exposure to wildfire smoke.

However, another found only limited evidence of excess cases after smoke exposure in wildfire-adjacent populations in California’s San Joaquin Valley.

These contrasting results show more research is needed to evaluate the infectious potential of wildfire smoke from this and other fungal and bacterial causes.

Staying safe

Much remains to be learned about the links between wildfires and infections, and the multiple pathways by which wildfires can increase the risk of certain infections.

There’s also a risk people gathering together after a disaster like this, such as in potentially overcrowded shelters, can increase the transmission of infections. We’ve seen this happen after previous natural disasters.

Despite the gaps in our knowledge, public health responses to wildfires should encompass infection prevention (such as through the provision of effective masks) and surveillance to enable early detection and effective management of any outbreaks.

Christine Carson, Senior Research Fellow, School of Medicine, The University of Western Australia and Leda Kobziar, Professor of Wildland Fire Science, University of Idaho

This article is republished from The Conversation under a Creative Commons license. Read the original article.