Improving cancer patient outcomes depends on expanding our understanding of basic cancer biology as well as improving patient access to the latest therapies.
The past decade has been an exciting one in both cancer research and clinical oncology. More and more tumors are being assessed for genetic drivers, many of which can now be targeted by precision therapies. The immune checkpoints hijacked by cancer cells to evade immune detection and elimination can now be blocked, and immunotherapy has become the standard of care for many cancers. Mortality rates continue to fall, and many patients now manage cancers as something of a chronic disease when they would have faced poor prognoses not long ago.
That success was celebrated in full measure at the recent 2023 American Association for Cancer Research (AACR) annual meeting I attended in Orlando, Fla. On a smaller scale, it was also celebrated at the Maine Cancer Genomics Initiative (MCGI) Forum held just prior, which showcased the success of MCGI in bringing precision oncology to all of Maine. And yet, at neither meeting was there complacency, and speakers fully acknowledged how much work there is still to do.
“Doing more of what we have today is not enough,” said National Cancer Institute Director Monica Bertagnolli, M.D., at AACR. “We need much more to cover the last mile.”
What is the last mile? For one, new therapies yield spectacular successes for some patients, but not all or even most. Combination strategies that shut down multiple cancer growth pathways limit recurrence in only some cancers some of the time, and side effects can be severe. There are specific cancers that remain difficult or impossible to treat. And not all patients can access the best care available.
So how can cancer research inform the next wave of progress for oncology and start covering that last mile, so to speak? How can that progress be provided to as many patients as possible? In summary, to borrow from the AACR meeting title, what is advancing the frontiers of cancer science and medicine, both in the lab and in the lives of patients?
Embracing the lessons of cancer biology
Standard chemotherapies and radiation work by targeting quickly dividing cells. It is a sledgehammer approach that kills most — but far from all — malignant cells, and it also kills normal cells with regular turnover such as hair follicular cells and the cells lining the GI tract. Targeted therapies and immunotherapies can be more effective than broad application chemotherapies and less toxic for healthy cells and tissues. Precise treatment option efficacies remain variable and pack a punch with severe toxicities leading to side effects still affecting too many patients. The key to improving the situation likely involves returning once again to the minutiae of cancer biology. If a massive meeting like AACR can have a theme, perhaps this year’s for me was delving ever deeper into the molecular details of cancer and individual human variation that previously had to be glossed over to some degree.
Like standard-of-care treatments, cancer research also had to be generalized. Researchers focused on cancer cell lines largely cultured in vitro, outside of the body and absent of the interactions with surrounding cells and tissues. They learned a lot about how cancer cells differ from normal cells and what might be targeted therapeutically, but they understood little of the dynamic environments in which tumors emerge and grow. Now, research capabilities provide the ability to look at cancers cell by cell, to see how they evolve and form different sub-populations even within the same tumor. Researchers can investigate the tumor microenvironment within the patient and determine how “normal” cells surrounding the tumor, including immune cells, are hijacked to support its formation and growth. Now with the capability to look at cells in patients and engineer them in model organisms such as mice, they can also investigate ways to strip tumors of their acquired protection.
The perspective of looking at the patient tumor microenvironment and cancer cells in a holistic way emphasizes the fact that cancers vary significantly from person to person. To a certain extent each cancer case is unique. While it’s not possible to tailor therapies for each individual, it is possible to look at distinct patient characteristics — normal cell genomics, microbiome, immune traits and more — that may affect response to therapies. The key to further improving clinical oncology may therefore rest in a better understanding of the biological nuances of patient traits in concert with the molecular processes underlying the growth of the cancer cells themselves. As the AACR sessions made clear, researchers are hard at work investigating the interplay between tumors and their environments, including therapy responses, and how it affects cancer progression. Changing the dynamics of these interactions may well provide a new way to make cancer cells more vulnerable, increasing the effectiveness of current therapies as well as providing new therapeutic strategies.
Access to the best cancer care
Another theme that emerged at both meetings was that current gains in cancer therapies and care are not available to all patients. Future clinical progress needs to be made more accessible. After all, what good is a cancer research breakthrough if few patients ultimately benefit from it? It was of particular concern at the MCGI Forum, as Maine provides a good testing ground for how to provide wider delivery of advanced care with particular emphasis on reaching rural populations. All Maine oncology practices now work with MCGI, providing genomic tumor testing, genomic tumor board consultation and access to national clinical trials to patients throughout the state. And yet, the patient population is widely scattered, may have lower incomes, and the logistics of care — transportation, cost, missed work and so on — is still a barrier for many. Also, few patients know about the complexities of molecularly targeted therapeutic strategies and immunotherapies, so education and engagement remain vital, yet sometimes overlooked, aspects of current cancer care.
MCGI is serving as a test case for the larger national (and international) effort to expand access to the latest advances in cancer care. Their data includes patient and physician perspectives on precision oncology, incorporating both their understanding of it and how positively or negatively they view it. The program studies how factors such as rurality, socioeconomic status and educational background influence patient willingness to participate. The Forum included sessions on how to integrate patient perspectives and experiences into precision care to provide a better understanding of side effects and toxicities — including financial toxicity — and achieving the best patient outcomes through shared decision making. Other speakers addressed the challenges of conducting clinical trials in rural areas, finding ways to bridge the gaps, and increase the feasibility of participation for patients with logistical and financial barriers.
While the complexities of cancer and human biology may seem far removed from the day-to-day struggles of cancer patients looking to receive the best care, both play significant roles in the future success of oncology. With the tools researchers now have, I expect the coming decade to be even more exciting for cancer care than the last. While no blockbuster drugs that work for a wide swath of patients are on the horizon, targeted therapies will be increasingly effective for more cancers and have fewer side effects. The same holds true for immunotherapies, as researchers and clinicians fine-tune the precarious balance between sufficient activation to kill cancer and overactivation and toxicity. But in many ways the efforts of initiatives such as MCGI are just as important, as clinicians and other medical professionals learn how to provide better access and engagement for patients who can most benefit from the latest research advances. Both are essential for better patient outcomes and for covering that last mile in cancer care.