NEW YORK – At the American Association for Cancer Research's annual meeting slated to take place in San Diego from April 5 to 10, researchers will shed further light on complex tumor biology and share data on novel drugs and tests that inform more precise treatment strategies.
According to Keith Flaherty, a program committee chair for the AACR annual meeting and director of clinical research at Mass General Cancer Center, the meeting's scientific program is organized around three main pillars: spatial profiling, data science and artificial intelligence, and drug chemistry platforms.
These scientific advances underlie much of the early-phase clinical studies scientists are presenting at AACR, which Flaherty said highlights how different areas of cancer research coming together results in better treatments.
"The plenary sessions and some of the organized sessions are where we really tried to focus on intersectionality of research disciplines because we've seen a big uptick of disciplines that were [previously] more siloed [but] are now colliding," Flaherty said. "We've tried to highlight examples of groups that are producing serious impactful new discoveries that are coming from those intersections."
Spotlighting science
Advances in spatial biology and spatial analysis, one of the pillars of the scientific program, have yielded a better understanding of tumor biology, he said. Using spatial analysis, researchers can investigate the role of different cells within the tumor and its microenvironment, which helps them understand how the makeup of these cells and interactions between them are allowing the tumor to grow.
Several of the plenary sessions at AACR this year explore how these novel profiling methods have advanced what researchers know about tumor biology generally, while experts in other sessions will discuss how the data from spatial biology analysis can be used to identify new biomarkers for informing treatments like immunotherapy or how large spatial molecular profiling databases can help identify novel biomarker subgroups and drug targets.
"What we're seeing now is just an unleashing of data that comes from these analyses," Flaherty said. "When that analysis comes from carefully curated cohorts of patients focused on specific cancer types or a specific population within a cancer type who are receiving a specific therapy, researchers are using these methods to try to understand the way in which those therapies affect the complex ecosystem of tumors."
Data science and AI will be another big focus area at this year's meeting. The program committee also highlighted this area of research with a plenary session in which researchers will talk about how AI is being used to support evidence generation, disparities research, and clinical trial design.
In other sessions, researchers will describe how they are applying AI to derive insights from large datasets, such as within the multi-institutional MOSAIC project that is drawing on multiomic data from more than 7,000 patients; how they are using AI-based computational pathology to supplement human expertise; and how AI-driven diagnostics tools are determining biomarker expression.
Flaherty also noted that the combination of spatial biology and AI is aiding research exploring differences in tumor biology across different racial and ethnic groups. "We've really tried to highlight the confluence of new molecular insights in underserved populations," he said. The insights gleaned from this research into the molecular differences in cancers among racial and ethnic groups could eventually lead to more personalized treatments tailored to these patient populations.
"What makes disparities research at the molecular level important and interesting is that different host populations can have different genetic determinants of risk for cancer or can have differences in terms of risk factor exposure," Flaherty said. "The field is getting insights now in terms of the molecular makeup and differences [across populations] and how those insights have ramifications both in terms of cancer early detection, intervention, and therapeutic development."
One session in this vein, for example, will shed light on molecular profiling in racial and ethnic minorities with breast cancer and will feature presentations on breast cancer tumor biology in patients of African ancestry and on the tumor and immune microenvironment of triple-negative breast cancer in a diverse cohort.
The final pillar of this year's scientific program is around drug chemistry platforms and novel drug modalities, such as protein degraders and molecular glues. Flaherty added that advances in drug chemistry have permeated the whole field, affecting how researchers identify new targets and how they drug those targets.
In this area, the AACR program features sessions about the design of new antibody-drug conjugates, the identification and optimization of protein degraders and inhibitors, efforts to drug cancer-related transcription factors, and other new therapeutic discoveries.
"All of this fits in the broad realm of beginning to be able to drug what we used to refer to as undruggable targets," Flaherty explained. "We're witnessing this massive expansion in terms of the fraction of the proteome that we can now actually deliver drugs against. There's this multi-prong drug chemistry advancement piece that is hitting the cancer field more so than any other therapeutic area, and it was irresistible for us to feature it at this meeting."
Translating science to clinical studies
Many of the scientific advances that AACR decides to showcase eventually do reach the clinic, and this year's program contains many opportunities to see how such basic research has led to new treatment or diagnostics.
Shivaani Kummar, co-chair of the AACR annual meeting clinical trials committee and codirector of the center for experimental therapeutics at Oregon Health & Science University's Knight Cancer Institute, said the 260 clinical trials abstracts accepted this year cover a wide range of therapeutics.
She highlighted research at this year's meeting that showcases investigational small molecules, antibody-drug conjugates, bispecific antibodies, cell therapies, and cancer vaccines. "What stands out is that [the program] covers therapies that go from targeting molecular abnormalities within the cancer cells to targeting the immune system and the tumor microenvironment," she said.
Scientists will present data on drugs targeting well-characterized tumor biomarkers, such as KRAS G12C mutations, PD-L1 expression, HER2 expression, and DNA damage repair pathways. The program features data readouts on novel therapeutic strategies, such as those targeting potential resistance markers GSTP and C797S in lung cancer.
The AACR program organizers have also included presentations on the activity of CAR T-cell therapies in solid tumors, including in ovarian cancer and pediatric solid tumors, and on the development of cancer vaccines, Kummar said. "We have the whole gamut, and that's a reflection of where … oncology drug development is going," Kummar said. "There's not just one way to treat this disease."
Flaherty noted that AACR's aim over the past few years has been to increase representation of early-phase clinical studies at the meeting to illustrate how basic lab and scientific work translates to the clinic, adding that the meeting's focus will always be on the scientific side.
"Time and again there are early-phase trials where the results are so clearly impactful that it's just a matter of time and more investigation before these will be [US Food and Drug Administration] approved drugs," he said. "Some people think of early-phase trials as just interesting, and not so clinically relevant. But more and more, we see [early-phase trials] that are quite obviously clinically relevant because they're clearly going to become FDA-approved therapies."