Cancer Prevention Prioritized at AACR Annual Meeting and a New Working Group

While preventive efforts have made great strides in reducing mortality from noncommunicable diseases, particularly cardiovascular pathologies, cancer is often diagnosed at advanced or even metastatic stages. Screening methods have led to earlier diagnosis and improved prognosis for some tumors; however, early detection is still challenging for many malignancies, and the value of screening has been debated for some cancer types. Targeted and immune therapies have emerged as powerful weapons. Still, for a large number of neoplasms – including pancreas, liver, lung, esophagus, brain, stomach, and ovary –survival at five years is still less than 50%, especially when patients present with late-stage disease (1). Furthermore, treating patients with targeted and immune therapies places a heavy economic burden on the health system. Progress in preventing cancer is urgent, with the number of cases currently rising extremely rapidly, due to increases in the population and longer life spans. The world population is close to 8 billion (2022) and is estimated to reach 8.5 billion by 2030 and almost 9.7 billion by 2050 (2).

Improving preventive measures for one disease can also protect against the onset or severity of another, as was shown during the COVID-19 pandemic. At an individual level, a person's “general health” was crucial in determining their fate after a SARS-CoV-2 infection. This was apparent in the differences on how COVID-19 impacted mortality rates: hypertension, obesity, type 2 diabetes, ischemic heart disease, and heart failure influenced disease outcome, with 82% of deceased patients showing two or more comorbidities.

Many cancers (over 30%) can be prevented by lifestyle, by avoiding risk factors such as tobacco use, excessive UV exposure, infectious agents, as well as poor dietary habits, lack of exercise, overweight, and obesity. Behavioral studies suggest that promoting healthy dietary habits and exercise can be a successful strategy; these measures can also protect or mitigate diabetes, metabolic disorders, and obesity. Genetic counseling in case of genetic predisposition and screening programs can help hindering or detecting certain types of cancer before signs or symptoms appear. In this complex scenario, stopping cancer before it starts or, in the second instance, before it becomes fatal, in a prevention or interception setting, remains a challenging task.

Molecular techniques and “big data” are opening up new avenues for efforts aimed at decreasing cancer incidence and death, which were presented at the 2022 AACR Meeting.

The American Association for Cancer Research was founded in 1907 at the beginning of a new era, aware of cancer as a treatable disease. A focus on prevention-related topics was always part of the AACR misson, thanks to four of the 11 initial founders: Harvey R. Gaylord, Robert B. Greenough, Leo Loeb, and Ernest Tyzzer, who were interested respectively in cancer etiology and immunology, cancer epidemiology, cancer hereditary factors, viral causes of cancer, and genetic factors of neoplasia.

The AACR journal Cancer Epidemiology, Biomarkers & Prevention was launched in 1991; years later, in 2008, the organization premiered its first journal focused purely on prevention: Cancer Prevention Research (CaPR).

Several dedicated Annual AACR International Conferences on Frontiers in Cancer Prevention Research have been organized through the years, and an AACR Cancer Prevention Summit was held in 2016, leading to a pivotal White Paper in CaPR (3) and a related report in Clinical Cancer Research (4).

The 2022 annual meeting of the AACR was held in New Orleans from 8 – 13 April: 15,000 researchers participated in person – with more than 4,000 attending virtually. More than 70 countries were represented. The theme of the meeting, was “Decoding cancer complexity, integrating science and transforming patient outcomes” and had several highlights on prevention, risk detection, and early diagnosis.

The plenary session on Saturday, April 9 centered on Precancer Discovery Science, with the presentation on “Transforming early detection and interception via a pre-cancer atlas” by Avrum Spira. The PreCancer Atlas (PCA) is a histologic and multi-omic mapping strategy over time and space to provide a detailed molecular, cellular, and structural characterization of premalignant lesions and how they evolve into invasive tumors, which was a priority of the 2016 Summit and is now an available tool (5).

The use of genomics to transform early detection and interception, moving from population to personalized prevention was explained by Rebecca Fitzgerald (6), and Susan M. Domchek (7).

This plenary was preceded by an educational session on Precision Strategies for Cancer Risk Reduction, which was chaired by Neil M Iyengar (8), where Graham A. Colditz (9) highlighted opportunities to build a knowledge continuum with the epidemiologists to advance cancer precision prevention through optimizing data usage and improved risk stratification.

The well-attended Opening Plenary Session was on “Decoding Cancer Complexity, Integrating Science, Transforming Patient Outcomes”, chaired by Marcia R. Cruz-Correa, where Nickolas Papadopoulos (10) explored the progress in techniques and strategies for multicancer early detection. This resides in the possibility given by the increasingly sophisticated techniques to detect even a few altered cells or small changes in metabolites, circulating or in precancerous districts. Minimally invasive molecular biomarkers can be applied to the early detection of multiple cancers. The use of microbiome studies to measure risk through microbiota signatures, metagenomics but also metabolism, was a recurrent theme. One example was a discussion of genotoxic gut bacterial metabolites and their roles in colorectal cancer initiation, presented by Jason M. Crawford (11) in the Opening Plenary. Bioactive microbial metabolites can impact host physiology and multiple biologically relevant host-microbiota metabolome interactions can be detected in cancer.

A Minisymposium on “New Targets and Strategies for Prevention and Risk Reduction” revealed how molecular techniques can now be used for prevention and early detection. Of particular interest was the presentation of a panel of methylated DNA and protein markers for multicancer detection in plasma, presented by Hatim T. Allawi (12), and the detection of early-stage lung cancer in a biomarker isolation platform that enables simultaneous isolation and on-chip detection of cell-free DNA (cfDNA), extracellular vesicle RNA (EV-RNA), and EV-associated proteins, illustrated by Juan P. Hinestrosa (13).

Diet and adherence to a healthy lifestyle may confer significant benefit for cancer prevention and reduction in all-cause mortality, this is a leitmotif in epidemiology and also the focus of an Educational session led by Lewis C. Cantley (14) with Karen Voudsen (15) and Lorelei Mucci (16). Many other factors can impact cancer risk, which is a warning to consider a multifaceted molecular but also social approach. Health disparities – along gender, ethnic (16) rural–urban, and economic lines – are associated with disparities in prevention, which was the focus of a number of presentations. “Financial toxicity” (17) can limit access to healthy lifestyles as well as screening and early detection.

The link between stress responses and promoters of tumor growth took center stage at the Presidential Symposium, on “Aging, Stress, and Cancer”. Electra Paskett was the opening speaker discussing how health outcomes can be the result of social and environmental determinants, rural–urban disparities, where stress is also an important factor at play. Patients living in “unfavorable” neighborhoods are likely to have worse cancer outcomes (18).

This year's recipient of the AACR award in “excellence in cancer epidemiology and prevention” in collaboration with the American Cancer Society was Susan E. Hankinson, who has devoted major efforts to exploring the use of urinary or blood markers and hormone levels to characterize exposure status in relation to breast cancer risk (19). This recognition accurately represents the rich tradition of epidemiology research pioneers who have really impacted our ability to prevent cancer. Susan Hankinson's studies have contributed significantly to the research of the etiology of breast cancer and to better understand some of the ways women can decrease their breast cancer risk, and, in women with the disease, improve their survival. She has led and worked widely with the Nurses’ Health Study (NHS) Research group and has evaluated a range of lifestyle factors (e.g., physical activity and body size, dietary intake, analgesic use) and circulating biomarkers (e.g., nutrients and hormones) in relation to risk and survival. She has provided some of the earliest data to indicate that blood estrogen and prolactin levels can predict breast cancer risk.

Opportunities to protect against metabolic syndrome and obesity – a major mediator of higher cancer risk among socially and economically deprived communities – were addressed by Victoria L. Seewaldt (20), who focused on insulin and insulin resistance as targets also for early intervention. Cornelia M. Ulrich took a closer look at the relationship between obesity, adiposity and cancer risk (21) in her presentation on “Does fat = fat? Eavesdropping on tumor–adipose tissue crosstalk in colorectal cancer”.

Seewaldt, Ulrich, and Michael Pollak, coeditor with Ray Dubois of the Cancer Prevention Research AACR journal (22), were the keynote speakers at the inaugural Cancer Prevention Working Group (CPWG) Town Hall Meeting and Networking Reception, where participants at the AACR Annual Meeting had the opportunity to exchange ideas and where programs were presented. Exercise, anti-inflammatory, antiobesity strategies, insulin lowering, metformin use (23, 24) were part of the rundown of the informative and informal evening.

Norman Sharpless, Director of the US National Cancer Institute (NCI), who has been succeeded in this responsibility by Douglas Lowy, highlighted the importance of the Cancer Moonshot mission (25), emphasizing the goal of a 50% reduction of cancer over the next 25 years, mission also aimed at prevention.

The last day, in a Session on Precancer, Philip E. Castle (26) debated on what is “precancer”: should we detect it, and if so, under what circumstances? Precision cancer prevention might not be effective in all populations, particularly in minoritized communities. A molecular-based approach to precancer can improve current cancer prevention interventions.

In the closing Plenary Session, “AACR Annual Meeting 2022 Highlights: Vision for the Future”, chaired by Marcia R. Cruz-Correa, Jennifer A. Doherty, a molecular epidemiologist (27) presented a summary of the research that had been shared during the conference on the topics of prevention, early detection, population sciences, and disparities research.

The feeling is that we are moving toward precision prevention, better tools for early detection and for risk assessment also through the use of Precancer Atlas, diagnostic strategies by investigating circulating cells, vesicles and DNA, and a broader awareness of the multifactorial approach to avoid cancer development.

Several AACR special meetings and the 2016 AACR Cancer Prevention Summit underlined through the years that most pivotal cancer prevention trials relied on clinical outcomes and took an extremely long time to complete, dissuading private investment. One problem in cancer prevention research has been low funding levels, which discourages investigators, particularly in their early careers from entering the field. It was therefore very motivating to see an entire session dedicated to “NCI Opportunities in Funding in Cancer Prevention and Control Clinical Trials”. Suggestions on how to plan Grant applications for cancer prevention, screening, and symptom management, and for behavioral interventions in cancer prevention and control, were offered by Brandy Heckman-Stoddard, and Susan Czajkowski.

Challenges that the scientific community is trying to overcome were the lack of validated preventive targets; insufficient diagnostics associated with identifying those at-risk populations most likely to respond to molecular preventive interventions; lack of sufficiently validated surrogate endpoints to define at-risk populations, prioritize key mechanisms, and accelerate developmental timelines. These and other needs have paved the way for the launch of the new AACR Working Group.

We are ahead in a mission that is now embraced by new stakeholders. On June 8, 2022, the US Centers for Disease Control and Prevention (CDC), the country's health protection agency, announced awards of US$215 million as first-year funding, under a US$1 billion investment plan over a 5 year period, with three national cancer prevention and control programs (28).

The AACR Cancer Prevention Working Group (CPWG) is the eighth and newest scientific working group of the AACR. It testifies to the AACR's dedication in supporting cancer prevention research.

The mission of the CPWG is to establish cancer prevention as a global priority through innovative science, integration of the latest technologies, improved levels of funding, and delivery of effective public education and awareness strategies. It provides a forum for communication and collaboration among basic, translational, and clinical scientists; physicians, nurses, and other health care providers; and cancer prevention experts in academia, industry, and government (29).

The Cancer Prevention Working Group (CPWG) will strive to accomplish its mission through several actions (Fig. 1). The CPWG Steering Committee is very comprehensive, with 28 members (30), which is an indication of how wide the field is and how diverse areas of expertise are required.

The members of the working group will collaborate to facilitate basic, translational, and clinical trans-disciplinary research aimed at promoting the understanding of cancer prevention science (28). Membership in the CPWG is free and open to all members of the AACR interested in cancer prevention and related scientific disciplines. Cooperation with the Population Science Working Group chaired by Andrew Chan will enhance the potential of decreasing the cancer burden.

Chan's pivotal work on cancer prevention has contributed to the evidence that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer. This has led to U.S. and international guidelines recommending aspirin for the primary prevention of colorectal cancer in specific populations (31).

Following the inception of the AACR's Molecular Epidemiology Working Group in 1999, the number of AACR scientific working groups has continued to expand to meet the needs of the cancer research community (28). Margaret Foti, chief executive officer of the AACR, personally announced the birth of the CPWG, dedicated to the vital area of cancer prevention research, confirming that: “The field of cancer prevention has been an area richly supported by the AACR since the organization's founding in 1907, with the leadership of several AACR Past Presidents. This new working group will ensure that the AACR remains at the leading edge of scientific advancements in cancer prevention, early detection, and interception” (29).

The mission of the AACR Cancer Prevention Working Group (CPWG) is to spotlight and strengthen awareness of cancer prevention as an essential strategy in cancer control and to establish cancer prevention as a global priority supported by improved funding, the very latest technologies, and best educational strategies (29). The AACR Cancer Prevention Working Group provides a forum for communication and collaboration among basic, translational, and clinical scientists, physicians, nurses, as well as surgeons, radiologists, and oncologists in academia, industry, and government, and with patient organizations. The group assists in facilitating trans-disciplinary research aimed at promoting the expansion and understanding of cancer prevention science (29).

Information about the Cancer Prevention Working Group include the instruction on how to become a member are visible at the website: https://www.aacr.org/professionals/membership/scientific-working-groups/cancer-prevention-working-group/.

CaPR invites to submit relevant publications with a fee discount for the working group members: https://www.aacr.org/professionals/membership/scientific-working-groups/cancer-prevention-working-group/publication-discount-for-cancer-prevention-working-group/.

No disclosures were reported.

The author would like to thank Cornelia Ulrich (Salt Lake City, UT) and Anna Wagstaff (Cancerworld, Europe) for critical reading of the manuscript and for helpful advice.