By Rich Soll, Senior Advisor, Strategic Initiatives, WuXi AppTec (@richsollwx) and WuXi AppTec Content Team
Cancer is one of the world’s leading causes of death and is a persistent challenge for the global healthcare industry. It comes in many forms, defying an easy “one size fits all” solution. Progress has been uneven, with some cancers completely curable and others resisting our best attempts at treatment.
One key locus in the battle against cancer is the Dana Farber Cancer Institute. With more than 5,000 staff, faculty, and clinicians Dana Farber blends patient-centric treatment, teaching, training, and cutting-edge research. It is the number one pediatric oncology center in the US.
The institute’s research budget is about $480M and only 40 percent is government funded – the remainder comes from the private sector and philanthropy. Yet the Institute receives more money from the National Cancer Institute than any other cancer center and its publications are cited two to three times more than its peers.
Heading up Dana Farber is CEO Laurie Glimcher, MD., a distinguished immuno-oncology (IO) researcher, with present or past chaired-appointments at Harvard Medical School and Harvard School of Public Health and scientific and executive positions at Weill Cornell Medicine. She was also one of the founders of Quentis Therapeutics, which specializes in IO. She currently serves on the boards of GlaxoSmithKline and the Waters Corporation and on several scientific advisory boards.
Glimcher is widely recognized as a staunch advocate for increasing both basic and translational cancer research, reducing the complexity of the U.S. healthcare system, and promoting women in science.
Rich Soll and the WuXi AppTec Content Team recently discussed the battle against cancer, the complexity and scale of funding cancer research, and the future of cancer diagnosis and treatment with Glimcher. She identified two key barriers to delivering better medicines faster and cheaper to cancer patients.
“First is research; it’s at the core of innovation yet government funding is insufficient,” Glimcher stated.
“The whole cancer field has broken open over the last couple of decades. It’s logarithmically better. And I think the next 10 years could be even more impressive, but that won’t happen if we don’t have the money.”
“The other barrier is the complexity of the U.S. healthcare system,” Glimcher stressed.
“Any solution needs to preserve incentives for innovation. If you’re a teaching hospital you’re not just seeing patients, you are the source of the discoveries — research and the training of the next generation of scientists and physicians. So, our costs are just going to be higher, because we are responsible for all the teaching and all the research as well.”
She views the challenge as more than just a question of system design. The social determinants of health are, in her view, the key.
“It’s hard to compare us to Scandinavian countries or Japan because these countries are extremely homogenous. Immigration is one of America’s strengths. But it also has created a lot of inequality,” Glimcher said.
Social inequalities are, in her view, a huge contributor to difference in healthcare outcomes, and any reform needs to address this reality.
Turning to cancer specifically, Glimcher views the current situation positively and is very optimistic about the future for two reasons.
“We are at the tip of the iceberg,” she exclaimed.
The first reason she cited is precision medicine. Being able to identify the majority of cancer-causing mutations is a huge step forward. This is because mutation identification is a critical part of developing drugs that disrupt cancers. Specific examples she cited were EGFR receptor blockers, drugs, which target the ALK kinase, Herceptin and the first targeted cancer drugs that are cancer agnostic.
But she made it clear there are still challenges. “The tumor is smarter than we are. It will eventually mutate again to circumvent the therapy,” Glimcher said.
This observation led to combination therapy, the use of multiple drugs to treat a condition. Glimcher cited its success in moving HIV from a death sentence to a manageable condition. However, testing is the main challenge here.
“We need to be able to test combinations of drugs in people very quickly— but how many clinical trials can you do? We do over 1000 clinical trials at Dana Farber,” Glimcher said. “The whole world can’t do enough clinical trials, and patients don’t have time to wait either.”
The second major recent development in cancer treatment is immuno-oncology therapies (IO). Currently, IO therapy is effective in about 10 tumors.
“The problem is only about 30 or 40 percent of patients with these tumor types will respond. And then there are a lot of tumors that so far have been totally unresponsive to IO therapy,” Glimcher said.
“We want to be able to treat 100% of patients with IO therapies, not just 20% of patients. I have confidence we’re going to come up with many more IO therapies.”
She shared a vision for what the future could look like.
“For a patient who walks in the door, we need to quickly analyze their cancer— immunoprofiles, genomics, radiology, pathology that had been digitized by machine learning, metabolomics and structuring the medical records, and then be able to take their tumors and the surrounding tumor microenvironment, quickly make organoids out of it (human tissue, complete with micro-environment, an all-human tissue testing approach), and test a wide variety of drug combinations,” she said.
She contrasted this with the state of things now, where patients may be able to join only a handful of clinical trials and deciding which are best is seldom easy.
To solve this requires diligent data collection.
“We need to get to where we can say, ‘Oh, we’ve seen this in 1000 other patients with lung cancer, and given your genomics, immunoprofile, and pathology, drug A is highly likely to work for you while drug B, while also likely to give you strong results, is highly likely to cause you to develop very serious toxicity from it.’ That’s something we just can’t do now,” Glimcher said.
Getting there, however, is one of Dana Farber’s highest strategic priorities, alongside developing the next generation of targeted medicines, combination therapy, and discovering new targets for IO therapy.
To accomplish this goal, Glimcher views improving cancer testing and evaluation as an important priority.
Testing and evaluation helps reduce risk, whether it’s in vivo or in animal models. But in her view, we’ve reached an impasse regarding animal models.
“We can cure cancer in mice, but it doesn’t always translate to cancers in humans,” Glimcher said. “Animal models are improving, but they’re still not great. If we could generate all human ex-vivo assays that were predictive for patients, it would be a huge leap forward.”
Glimcher also contrasted the progress made in adult cancers vs. children.
“Pediatric CNS tumors and sarcomas are different from adults. Children don’t get a lot of single mutations that drive their tumors, rather their cancers often arise from fusion proteins or epigenetic alterations that drive the cancers. It’s our responsibility to focus on them too,” Glimcher explained.
Cancer detection is an important component in achieving this data-driven vision. This includes early diagnosis, early detection of minimal residual disease, and detection of early relapse. Early detection requires being able to identify a very small number of cells in a liquid biopsy. She acknowledged it’s a challenge, although some companies like GRAIL are, in her view, making good progress.
Missing residual disease continues to be a challenge; she cited several instances where a patient’s cancer was supposedly cured, but then many years later it is discovered that this is not the case, and instead the cancer had widely metastasized. Preventing this requires an ability to detect trace cancer cells that may get missed.
Finally, early relapse is also an issue. Glimcher stated that 15-20% of women who are supposedly cured of breast cancer will eventually present with metastatic disease – monitoring is thus key.
“Those are some of our strategic priorities,” she said. “And we’re actively trying to harness AI and machine learning to collect the data we need. We’re structuring our medical charts, pathology and radiology, digitizing and then analyzing them.”
One of Dana Farber’s most recent partnerships is with Deerfield Management. Announced in November 2018, the $80 million deal created a Center for Protein Degradation at Dana Farber. Protein degradation is a promising but relatively new approach to treatment.
“Out of all the 20,000 or so proteins we have, only about 750 or 1000 have been actually targeted by drugs,” Glimcher shared. “So there’s huge room for growth.”
She went on to say that innovative partnerships like this are key to advancing science and in speeding up the development of successful treatments.
Cancer is one of the disease areas that receives the most attention and funding, but historically the success rate has been low. Glimcher addressed some of the key factors needed to improve outcomes: better pathway and target validation and more predictable models both in-vitro and in-vivo.
Glimcher acknowledged that the nature of cancer itself is also responsible for the difficulties in developing a treatment.
“Most cancers are silent until they’ve metastasized. Cancers are all different from each other. Seventy percent of the time they don’t present until they’ve already spread,” she said.
This is why she views early detection as vitally important. Her view is that if we can reliably detect cancers at Stage 1, we can almost always cure them. Even at Stage 2, cures are sometimes possible. But, citing pancreatic cancer as a typical example, most cancers don’t get detected until they have spread everywhere – contributing to the difficulties treating cancer.
While a cure is desirable, it continues to prove elusive.
“Of course, it would be great to cure all cancers,” Glimcher stated. “And for some cancers we’ve gotten there. But I’d honestly be extremely happy if we could make them chronic diseases like we’ve done for HIV.”
“We may not get rid of every single cancer cell, but they’re quiescent, and maybe they’ll pop up in a little bit and then we detect them really early and treat again, and people can live for years and years,” she said.
Glimcher concluded with a personal perspective on leading Dana Farber.
“The future is incredibly bright here. Our staff is 50% clinicians, 50% researchers; this split is unique among cancer centers. 90% of our clinicians have scholarly interests,” Glimcher said.
“I get hundreds of letters from patients and they’re almost uniformly positive, which is amazing since people usually write to CEOs to complain. It’s like a family here, we couldn’t have asked for better care. Being a CEO of a hospital can be tough; the amazing people here and the work we do, that’s what keeps me motivated to do my best every day.”