AACR 2022: Researchers Reflect on Recent Gains and the Future of Cancer Research

Major cancer conference featured a number of notable sessions on breast cancer and BCRF investigators

This April’s hybrid American Association for Cancer Research (AACR) Annual Meeting once again convened tens of thousands of the world’s top cancer researchers for several days of enriching scientific presentations, posters, and collaboration. Many BCRF investigators attended the conference in person and virtually to give lectures and serve as panelists discussing breast and other cancers, and seven grantees received some of the event’s most prestigious awards.

Being one of the largest cancer research conferences in the world, AACR’s annual meeting is multidisciplinary and not focused on any one cancer. Sessions and lectures cover every aspect of cancer research, from basic science to news from clinical trials. The event included two inaugural sessions dedicated to pre-cancer discovery and tumor evolution, and several dedicated to cancer disparities.

This year’s conference included several significant takeaways from the breast cancer research field. After attending the conference virtually, the BCRF team reflected on noteworthy sessions, updates from breast cancer clinical trials, and a closing presentation that offered a moment to reflect on progress made possible by research.

New sessions on pre-cancer and tumor evolution

In 2022, AACR held the first-ever sessions in pre-cancer discovery and tumor evolution—emerging foci that will allow the identification of cells most likely to become cancerous or metastasize. Several presenters—including BCRF investigators—summarized current progress in these areas.

BCRF investigator Dr. Christina Curtis gave an award lecture on pre-cancer biology. In addition, a larger session highlighted some of the groundbreaking research in this area, including efforts to define gene mutations that may play a role in cancer initiation and develop a “pre-cancer atlas” to map the cellular and molecular events that cause normal cells to become cancerous.

Fellow BCRF investigator Dr. Susan Domchek discussed ongoing studies and clinical trials in “cancer interception”—stopping carcinogenesis at the earliest possible point—to reset a person’s cancer risk. In addition, Dr. Domchek explained how vaccines may play a significant role in cancer interception (a strategy that is being tested in two separate BCRF-funded projects led by Drs. Mary Disis and Robert Vonderheide, as BCRF covered here). While much remains to be done, these are nevertheless exciting avenues of research.

Normal tissues are a collection of diverse cells or cell groups called clones, each of which can evolve over time to cause cancer—a process called tumor evolution. In the inaugural AACR session on this topic, Dr. Peter J. Campbell of the Wellcome Trust Sanger Institute described his research that found mutations in normal tissue occur over time and breast cells specifically accumulate about 13 mutations every year of life. Dr. Nicholas Navin of MD Anderson Cancer Center discussed how single-cell DNA and RNA sequencing technologies can uncover changes in individual cells within a tissue or those in a specific clone that lead to tumor formation.

BCRF investigator Dr. Charles Swanton, who studies several types of cancer, including breast, described his work in lung cancer that showed tumors evolving from many subclones have poorer outcomes and are more likely to metastasize than tumors from a single subclone. These results deepen our understanding of tumor evolution and may provide strategic avenues for improving treatment and prevention for breast, lung, and other cancers.

Reflecting on the ‘10 Ms’ of cancer research now

The meeting concluded with a session highlighting recent gains in cancer research and reflecting on where the field is going. Breast cancer researcher Dr. Danny Welch of the University of Kansas Cancer Center began his talk by acknowledging how the scientific community has made remarkable progress driving cancer research forward—even in the face of a global pandemic.

He then discussed major themes that emerged from the meeting, all beginning with the letter M: microenvironment, microbiome, metabolism, mitochondria, metastasis, machine learning, mindset, mutualism, meaning, and medicines. Dr. Welch described how these themes are intertwined and contribute to the complexity of cancer, and how researchers are harnessing new technologies and collaborating to unravel these complexities. While Dr. Welch’s talk was not specifically focused on breast cancer research, these “Ms” are all applicable to the field. Among them:

• Tumor cells are surrounded by other cells and molecules that all interact to form the tumor microenvironment. By mapping tumor microenvironments, researchers can reveal characteristics about specific cancer subtypes and metastases and ultimately open the door for precision cancer prevention.
• The microbiome, the collection of billions of microbes that exist in and on the body, has been shown to influence tumor cells’ behavior and their microenvironment. Considering the role of the microbiome adds a new dimension to preventing and treating cancer.
• It has long been recognized that mitochondria (structures inside cells) produce precursors for molecules that are essential for cellular function. We are now understanding that their genetics have more influence on tumor behavior than was previously known.
• Researchers have discovered new hallmarks of metastasis in the last two years: Some cancer cells, but not all, have distinct characteristics that promote cancer’s spread; and tumor metastases express markers that are different from primary tumors and metastases in other locations. Investigators are capitalizing on these insights to specifically target metastasis.
• Machine learning algorithms, which analyze enormous amounts of multi-dimensional data, have led to advances in many areas including imaging, such as mammography, and enabled more accurate and earlier diagnoses as a result.

Dr. Welch closed by stressing the positive impact of collaboration across fields to bring together researchers that share a mutual goal to address cancer’s most difficult challenges. He also noted the importance of listening to and partnering with patients. “We want to give [research questions] added meaning so we can develop better medicines,” he said.

Notable highlights from cancer disparities sessions

AACR devoted several sessions to cancer disparities this year, which were best summarized by Dr. Lauren E. McCullough of Emory University in her talk: “Disparities by race are not simply a result of biology or access; there are multiple drivers from cell to society.”

Dr. Robert Winn of Virginia Commonwealth University referred to the “Znome” or “ZNA” to emphasize that an individual’s home address is an important contributor to cancer outcomes, and this is manifested in Dr. McCullough’s work assessing the impact of neighborhood redlining. She and her team found that individuals living in contemporary redlined areas in Atlanta are 60 percent more likely to die from breast cancer. Redlined neighborhoods not only have reduced real estate investment, but residents experience poorer air quality, increased intra-urban heat, lack of greenspace, and food deserts. Dr. McCullough’s work has expanded to reveal how these stressors correlate with biologic changes that can promote poor outcomes.

One area of focus for BCRF researcher Dr. Electra Paskett is the impact of social stresses on cancer, specifically in the Appalachia region of the United States. In a talk, she emphasized the need for a shift from blaming poor health outcomes on an individual to instead exploring factors like insurance, social and physical context, genetic pathways, and the environment.

As our understanding of the drivers of cancer disparities continues to unfold, researchers are developing interventions designed to counter them. Dr. Cheryl Willman from the Mayo Clinic described a novel initiative to address the dearth of genomic data on cancers arising in American Indians (AI), who experience the nation’s poorest cancer outcomes. This program, co-designed with tribal advisory councils, aims to collect biospecimens and data (lifestyle and environmental) from approximately 1,000 AI cancer patients in the American Southwest and uses culturally appropriate consents that incorporate indigenous languages and art. Participants will have access to genetic counselors along with real-time return of their data, so that this information can be used for therapeutic interventions.

News from breast cancer clinical trials

In the clinical trials space, major highlights presented by Dr. Lillian Siu from the Princess Margaret Cancer Centre included several studies of DNA-damage response (DDR) agents such as PARP inhibitors currently used to treat breast cancer. Dr. Siu summarized promising early data from the ongoing PETRA study testing a highly specific PARP inhibitor in patients with BRCA, PALB2, or RAD51 mutations. She stressed the importance of expanding the use of DDR agents beyond PARP inhibitors and referenced several preclinical studies presented at AACR that are testing new forms of this therapy.

Dr. Siu also covered the rapid expansion of antibody-drug conjugates, a promising set of therapies with some success in HER2-positive and triple-negative breast cancer. As Dr. Siu pointed out, researchers are steadily working to improve current therapies, develop new therapies, and characterize biomarkers to identify patients who will benefit. 

The presentations at AACR highlight the many advancements being made by BCRF researchers and others. BCRF looks forward to further progress that not only moves the needle in precision medicine, but that also deploys multiple cutting-edge strategies for cancer interception and advances our understanding of the biology of the precancerous state.