Over the past year, MD Anderson researchers and clinicians have investigated the gut microbiome, examined the earliest genesis of lung adenocarcinoma cells, tested new and improved therapies, and more. Their breakthroughs in cancer research continue to drive forward our mission to end cancer.

Here are 11 novel MD Anderson research highlights from last year.

1. Eating beans improves gut health, regulates immune and inflammatory processes in colorectal cancer survivors

The BE GONE trial examined the effects of adding one cup of cooked white navy beans per day to the diet of participants with a history of colorectal cancer. Carrie Daniel-MacDougall, Ph.D., associate professor of Epidemiology and director of MD Anderson’s Bionutrition Research Core, led the trial.

Participants saw an increase in beneficial bacteria and a decrease in harmful bacteria in their gut microbiome after eight weeks when incorporating the beans into their diet, compared to their diet without beans. Both diet and gut health, including microbiome balance, play a role in the prevention of inflammation, cancer and cardiovascular disease that impact the health and longevity of colorectal cancer survivors.

The study’s findings, published in eBioMedicine, highlight the importance of consistent and sustainable dietary changes. “Observing a shift in microbiome diversity with diet intervention alone is rare, and this study underscores the ability of a readily available prebiotic food to bring about such changes,” says Daniel-MacDougall.

2. PARP inhibitor plus immunotherapy lowers risk of endometrial cancer progression over chemotherapy alone

Compared to treatment with chemotherapy alone, adding durvalumab, an anti-PD-L1 monoclonal antibody, reduced the risk of disease progression or death in patients with newly diagnosed stage III-IV or recurrent endometrial cancer. Adding a PARP inhibitor called olaparib reduced the risk further.

Shannon Westin, M.D., professor of Gynecologic Oncology and Reproductive Medicine, presented findings from the Phase III DUO-E trial at the 2023 European Society for Medical Oncology (ESMO) Congress. The findings were also published in the Journal of Clinical Oncology.

3. Novel menin inhibitors show promise for patients with advanced acute myeloid leukemias

A multicenter Phase I clinical trial and a Phase I/II trial both showed promising results from novel therapies for the treatment of relapsed or refractory acute leukemia. Data from both trials were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

The Phase I trial, led by Elias Jabbour, M.D., professor of Leukemia, investigated the menin inhibitor JNJ-75276617 in leukemia with changes to the KMT2A or NPM1 gene. The Phase I/II trial led by Ghayas Issa, M.D., assistant professor of Leukemia, combined revumenib, a menin inhibitor, with the hypomethylating agent ASTX727 and the BCL-2 inhibitor venetoclax in patients who had changes to the KMT2A, NUP98 or NPM1 gene. Issa led an additional trial of revumenib, called AUGMENT-101, which was previously published in Nature and led to FDA approval of the drug for adults and pediatric patients with relapsed or refractory advanced acute leukemia with KMT2A gene rearrangements.

4. Changes in gut microbiome may influence cancer growth in other parts of the body

Interleukin-17 (IL-17) is a signaling protein linked to both regulating the balance of the gut microbiome and cancer progression. In preclinical models, removing the IL-17 receptor in the intestines led to an unbalanced gut microbiome and the growth of remote brain and pancreatic tumors. However, the effect was reversed by adding antibiotics that targeted the “bad” bacteria promoting tumor behavior.

The research, led by Florencia McAllister, M.D., professor of Gastrointestinal Medical Oncology and Genetics, and published in Cancer Cell, suggests a role for antibiotics or other interventions to maintain gut microbiome balance in trials with drugs targeting IL-17.

5. Vaccine demonstrates potential in delaying relapse of KRAS-mutated pancreatic and colorectal cancers

Published in Nature Medicine, results from the Phase I AMPLIFY-201 trial show the potential of the ELI-002 vaccine to prevent relapse of KRAS-mutated cancers.

ELI-002 is an off-the-shelf cancer vaccine that targets KRAS G12D and G12R-mutant cancers. It trains T cells to recognize KRAS mutations and eliminate the cancer cells that have them. Patients with pancreatic and colorectal cancer who were at high risk for relapse received the vaccine. 84% of patients showed T cell responses that were correlated with an 86% reduction in risk of relapse or death.

The results from this study, led by Shubham Pant, M.D., associate professor of Gastrointestinal Medical Oncology, have led to a Phase II trial with an updated version of the vaccine targeting additional KRAS mutations.

6. Study unravels the earliest cellular genesis of lung adenocarcinoma

Humam Kadara, Ph.D., professor of Translational Molecular Pathology, and Linghua Wang, M.D., Ph.D., associate professor of Genomic Medicine, led a team who built an atlas of around 250,000 lung epithelial cells. Using single-cell sequencing, they looked at genetic changes in individual cells from normal and cancerous tissue samples of the lung lining.

A key discovery was the identification of a novel cell state with KRAS mutations. A subset of alveolar cells, lung cells that help exchange gases, taken from normal lung tissue had KRAS mutations that led to lung adenocarcinoma in preclinical models.

“Our study provides unequivocal evidence that tumor cells do, indeed, arise from these intermediate cells, opening the door for new research avenues,” Kadara says of the research, which was published in Nature. “These findings are very exciting since they suggest that KRAS inhibitors could be clinically beneficial for treatment or even interception of primitive stages of lung adenocarcinoma.”

7. PARP1-selective inhibitor demonstrates early efficacy in breast cancers with DNA repair defects

The Phase I/II PETRA trial, led by Timothy Yap, M.B.B.S., Ph.D., professor of Investigational Cancer Therapeutics, evaluated a first-in-class PARP inhibitor, saruparib, for patients with homologous recombination repair-deficient breast cancers.

HRR-deficient cancer cells have changes that negatively impact their ability to repair DNA, which makes them more dependent on the PARP protein to repair damaged DNA. First-generation PARP inhibitors targeted two types of PARP protein, PARP1 and PARP2, whereas next-generation PARP inhibitors, like saruparib, target PARP1 only.

Saruparib had encouraging efficacy and an improved safety profile compared to first-generation PARP inhibitors. Following results presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, saruparib is being tested in a Phase III trial.

8. Pre- and post-surgical immunotherapy improves outcomes for patients with operable lung cancer

Patients who received nivolumab had significantly prolonged event-free survival and a 42% reduction in risk of lung cancer progression, recurrence or death, according to research led by principal investigator Tina Cascone, M.D., Ph.D., associate professor of Thoracic/Head & Neck Medical Oncology. The study examined adding nivolumab, a type of immunotherapy, before and after surgery. The results indicate perioperative immunotherapy effectively reduced the risk of relapse for the more than half of patients with operable non-small cell lung cancer.

Data from the Phase III CheckMate 77T study was initially presented at the 2023 European Society for Medical Oncology (ESMO) Congress and was published in the New England Journal of Medicine.

9. Proton therapy demonstrates advantages in Phase III head and neck cancer trial

A multicenter Phase III trial, led by Steven Frank, M.D., professor of Radiation Oncology, compared traditional intensity modulated radiation therapy (IMRT) to intensity modulated proton therapy (IMPT) for patients with head and neck cancer undergoing chemoradiation treatment.

IMPT was statistically as effective as IMRT at extending progression-free survival. Patients who received IMPT had less malnutrition, weight loss and feeding-tube dependence than those receiving IMRT.

Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, this was the largest randomized Phase III trial comparing IMPT to IMRT. “The results of this multi-center Phase III randomized trial provide evidence for IMPT as a new standard-of-care treatment approach for the management of head and neck tumors,” Frank says.

10. GPX4 and PARP co-inhibition may boost PARP inhibitor effectiveness in BRCA1-deficient cancers

BRCA1-deficient cancers and other cancers with impaired DNA repair mechanisms often respond well initially to PARP inhibitors, then develop resistance. In a study published in Cancer Discovery, researchers led by Boyi Gan, Ph.D., professor of Experimental Radiation Oncology, identified GPX4 co-inhibition as a possible therapeutic strategy to overcome PARP inhibitor resistance.

Glutathione peroxidase 4, or GPX4, is a protein that inhibits ferroptosis, a newly discovered type of cell death that depends on iron. In preclinical models, tumors derived from patients with BRCA1-mutant breast cancer experiencing PARP inhibitor resistance had a higher sensitivity to co-inhibition by both PARP and GPX4.

11. CAR NK cells with CD28 costimulation improved cell persistence and antitumor activity

Researchers led by Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy, added CD28 costimulation to chimeric antigen receptor (CAR) natural killer (NK) cells targeting CD70 in preclinical models of solid tumors and hematologic cancers.

To target CD70, CAR NK cells have a protein receptor called CD27 added to their surface. It allows them to recognize and target cancer cells expressing CD70. To evaluate costimulatory options, researchers in the Rezvani Lab tried adding CD28, another type of protein receptor.

Adding CD28 costimulation enhanced the CAR NK cells’ efficacy and persistence, improving antitumor activity. The research, published in Cancer Discovery, led to the initiation of first-in-human Phase I/II clinical trials to assess CAR27 NK cells with CD28 costimulation.

“Based on the innate anti-tumor activity of NK cells against cancer and the potential of CD70 as a target antigen, CD70-targeting CAR NK cells hold significant promise as an effective treatment for many solid tumors,” says Rezvani.

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