Mark Polizzotto: translation into practice

In May 2020, the U.S. Food and Drug Administration made an accelerated approval of pomalidomide for Kaposi sarcoma. It was the first new treatment for this cancer in over 20 years.

The basis of this approval was an early phase clinical trial spearheaded by Dr Mark Polizzotto, based at the U.S. National Cancer Institute at the time.

“I’m very proud of the work,” said Polizzotto, who recently joined the John Curtin School of Medical Research (JCSMR) as Professor of Medicine, “It is novel therapy for a neglected but important cancer. Importantly, it is an oral drug, so it is readily deliverable, and it is now off patent so it can be quite inexpensive.”

Working with his mentor, Dr Robert Yarchoan, in the United States, Professor Polizzotto started that trial in 2012 and finished it by 2016.

But beyond completing and publishing the trial, they worked with the company that made pomalidomide (Celgene, now a part of Bristol Myers Squibb) to get it registered.

“Registration makes a big difference in terms of patient access,” said Professor Polizzotto.

For years, Professor Polizzotto has focused his research on developing new therapies to prevent and treat cancers.

At the core of his interests are infection-related cancers, a category of cancers attributable to infectious pathogens including certain viruses.

Kaposi sarcoma, for instance, is caused by a virus called human herpesvirus 8. Seen most often in people living with HIV, this virus can cause malignant lesions when the immune system is compromised.

Data source: GLOBOCAN 2020; Image: IARC/ World Health Organization

“I found infection-related cancers biologically very interesting and also clinically important,” said Professor Polizzotto.

When he was a trainee in medicine, Professor Polizzotto worked at a hospital that cared for a large community of people with HIV.

At that time, treatments for HIV were much less effective than they are today. As a result, infection-related cancers became a significant burden for those with severe immunosuppression related to HIV.

Even today, while we have effective treatments for HIV, cancers remain a significant burden among people with HIV, particularly in less resourced settings.

Driven by a desire for new knowledge of cancer biology and better approaches to help his patients, he built his career at the interface between clinical practice and fundamental research.

“Each working week, I use tools developed through clinical science to care for people who are unwell, and then go back into the laboratory to contribute to the new science under development,” he said, “This is the most rewarding part of my work.”

But the same interface is where he noticed gaps to be closed and unmet needs to be addressed.

Even within well-resourced settings, participants in many clinical trials tend to be well-educated, white, and male. Meanwhile, populations such as women, children, and people from economically or socially marginalised communities, are often underrepresented.

“And that’s a problem because that doesn’t reflect the people whom we as clinicians are actually treating,” said Professor Polizzotto, “Our clinical population is much more diverse than our trials and we need trial data to ensure we are using the most appropriate treatments.”

That’s why he has been proactively advocating for the inclusion of marginalised groups in clinical trials. Over the years, he has put in efforts to bring individuals with HIV and those from culturally and linguistically diverse populations into studies of emerging agents.

In his opinion, the first critical step for clinical trialists to make is to ensure nobody is excluded from the trial without a good reason.

“I think it’s an obligation that we design trials that reflect as closely as possible the real world,” he noted.

Professor Mark Polizzotto holds a strong commitment to diversity and inclusion in clinical trials. Image: Gerd Altmann / Pixabay.

While it’s one thing to have an inclusive design, it’s quite another to go into the communities and engage the people.

Researchers need to establish diverse partnerships in the community, Professor Polizzotto suggested, and really involve people from the community at the earliest point when thinking about research.

As a leader of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), Professor Polizzotto spent half a decade working across regions, including West Africa and the Asia-Pacific, to develop trial infrastructure and get local people involved.

When COVID-19 turned into a pandemic, the capacity and trust they built during the years quickly stood out as the perfect basis for global COVID treatment trials.

“It’s one of the examples where work done in HIV has accelerated our approach to COVID,” Professor Polizzotto remarked, “It was a source of real satisfaction to me.”

Having witnessed the striking disparities in health resources across the world, Professor Polizzotto also considers it critical to bridge the gaps in human expertise between rich countries and less developed countries.

“The technology is only as good as the doctors and nurses and other people who can get it to a patient,” he stressed.

“There’s a great role for universities in having other individuals come here to study or supporting them in their own country to study and develop that expertise.”

Equally important, he said, is to encourage people from diverse backgrounds to be researchers. That way, more perspectives can be raised and considered when addressing a research problem with public health implications.

“I would like to see an environment where we both placed more societal value on medical research and made considered long-term investments in research and researchers. I think this is critical, particularly to support researchers from diverse backgrounds to develop sustainable careers.”

As a new group leader at JCSMR, Professor Polizzotto is committed to carrying on working around early phase drug development.

“My interests have always sat between cancer and effective infection and immunity, and those are among the great strengths of John Curtin,” he said.

To him, facilitating the translation of fundamental research findings into the clinic requires much effort in forming and strengthening connections.

“I think it’s very important to stay curious about what fundamental scientists are doing,” he said.

Whether it’s through shared Journal Clubs or shared clinical meetings, there should be something to build and enhance the bonds between fundamental researchers and clinicians.

“I’m hopeful of finding those connections and opportunities in different places across the School,” said Professor Polizzotto.

“Finding a shared language is actually not that easy,” he said, “But particularly in medicine, we can’t lose that connection.”