Driven by our mission to end cancer, MD Anderson researchers developed new therapies, analyzed vast data sets, solved medical mysteries and more over the last year. These breakthroughs across the spectrum of cancer research can make immediate impacts on the lives of patients and shape the future of cancer care.
To expand the reach of these transformational breakthroughs, MD Anderson increased its visibility at national industry conferences, such as the American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO) annual meetings, where MD Anderson experts shared their knowledge with other attendees.
In the Phase III COMMANDS trial, treatment with luspatercept improved red blood cell counts and erythroid responses compared to treatment with epoetin alfa in patients with myelodysplastic syndromes, allowing the majority to forgo regular blood transfusions. Luspatercept is a novel agent that enables late-stage red blood cell maturation and helps restore normal red blood cell creation. The study, led by Guillermo Garcia-Manero, M.D., was presented at the 2023 ASCO Annual Meeting.
“I am encouraged by these results, as luspatercept represents a transformative therapy that could become a new standard of care for patients with transfusion-dependent myelodysplastic syndromes,” Garcia-Manero says.
A multi-institutional team created the world’s largest and most comprehensive map of normal breast tissue, providing a new understanding of mammary biology that may help identify potential therapeutic targets for diseases including breast cancer. The publication was the culmination of a seven-year effort led by Nicholas Navin, Ph.D., on the MD Anderson side. Using single-cell and spatial genomic methods to profile more than 714,000 cells from 126 women, the Human Breast Cell Atlas, published in Nature, highlighted 12 major cell types and 58 biological cell states. It also identified differences based on ethnicity, age and menopausal status of healthy women.
“We expect this tool will be highly useful for anyone studying breast cancer and other diseases such as mastitis, as well as breast development and lactation failure,” Navin says.
Research led by Sapna Patel, M.D., showed that patients with high-risk melanoma who received the immunotherapy drug pembrolizumab both before and after surgery to remove cancerous tissue had a significantly lower recurrence risk compared to similar patients who received the drug only after surgery. Published in the New England Journal of Medicine, the results showed consistent benefits across age, sex, performance status and disease stage.
“It's not just what you give; it's when you give it,” Patels explains. “The S1801 study demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”
Researchers led by Betty Kim, M.D., Ph.D., developed a novel delivery system for messenger RNA (mRNA) using extracellular vesicles (EVs) that shows the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies. Published in Nature Biomedical Engineering, the researchers used this method to initiate and sustain collagen production for several months in the cells of photoaged skin in laboratory models. As the first therapy to demonstrate this ability, it represents a proof-of-concept for deploying the EV mRNA therapy which is now being explored in immunotherapy applications.
“Throughout decades of research with adjuvant and neoadjuvant chemotherapy, we only succeeded in increasing lung cancer cures by around 5%,” says Heymach. “This study has the potential to increase that percentage significantly.”
Researchers led by Katy Rezvani, M.D., Ph.D., developed a new approach for engineering natural killer (NK) cells with a second chimeric antigen receptor (CAR) to act as a logic gate, requiring two signals to eliminate a target cell. The study, published in Nature Medicine, demonstrated how these next-generation CAR NK cells improved tumor specificity and enhanced anti-tumor activity by overcoming a process called trogocytosis, which contributes to tumor escape and poor responses after CAR NK cell therapy.
Through single-cell analysis, researchers led by Linghua Wang, M.D., Ph.D., created a spatial map of tumor-infiltrating B cells and plasma cells in early-stage lung cancers, highlighting the roles these cells play in tumor development and treatment outcomes. Published in Cancer Discovery, the study represented the largest and most comprehensive single-cell atlas of its type at the time of publishing. The study revealed the importance of environmental factors, such as exposure to cigarette smoke, as well as how molecular features of the tumor contribute to the landscape of these cell types.
A Phase II trial led by Henry Kuerer, M.D., Ph.D., and published in Lancet Oncology demonstrated that patients with early-stage breast cancer who had a pathologic complete response to neoadjuvant chemotherapy may be able to skip surgery and receive standard radiation treatment with a low chance of disease recurrence.
“This research adds to growing evidence showing that newer drugs can completely eradicate cancer in some cases, and very early results show we can safely eliminate surgery in this select group of women with breast cancer,” Kuerer says.
In a preclinical study published in Nature, researchers uncovered a gene on the Y chromosome that is upregulated in KRAS-mutated colorectal cancer, increasing tumor cell invasiveness and reducing anti-tumor immunity in male patients. Led by Ronald DePinho, M.D., the study provided new insights into the longstanding mystery of molecular and cellular mechanisms that drive increased metastasis and poor prognosis in men with colorectal cancer previously attributed mainly to lifestyle differences and possibly sex hormones.
“We now have an actionable target meriting further investigation, providing a path to intercept that will change the natural history of the disease in men with KRAS-mutant colorectal cancer,” DePinho says.
Afamitresgene autoleucel (afami-cel), an adoptive T cell receptor therapy targeting the MAGE-A4 cancer antigen, achieved clinically significant results for patients with multiple solid tumor types in a Phase I clinical trial led by David Hong, M.D. The outcomes, published in Nature Medicine, were especially noteworthy in the subgroup of patients with synovial sarcoma, where afami-cel achieved an objective response rate of 44% compared to 24% across all cancer types.
A study published in Nature Cell Biology detailed a previously unexplained type of cell death called disulfidptosis, triggered when cells with high levels of the SLC7A11 protein are subjected to glucose starvation. Led by Boyi Gan, Ph.D., and Junjie Chen, Ph.D., the findings demonstrated that in preclinical models, treatment with glucose inhibitors induced disulfidptosis in cancer cells with high SLC7A11 expression, effectively suppressing tumor growth without significant toxicity in normal tissues. This discovery could open the door for new therapeutic strategies.
Led by Neeraj Saini, M.D., and Robert Jenq, M.D., researchers developed a machine-learning algorithm that can predict long-term response to CAR T therapy using microbiome-based biomarkers. The findings could help in optimizing patient selection or tailoring follow-up treatment. Published in Nature Medicine, the study examined B-cell lymphoma patients receiving CAR T cell therapy to better understand the complicated effects of broad-spectrum antibiotics given prior to the therapy to prevent infection.
The Phase I AUGMENT-101 trial, led by Ghayas Issa, M.D., showed that inhibiting menin with revumenib yielded encouraging responses for advanced acute leukemias with KMT2A rearrangements or mutant NPM1. Published in Nature, the study offered the first evidence showing the safety and clinical activity of menin inhibition in acute leukemia and demonstrated the potential for targeting scaffold proteins shown to be vulnerable points in specific cancers.
“The responses show that menin inhibitors may be a promising treatment option that is well tolerated by patients and could be the newest addition to successful targeted therapies for acute leukemia,” Issa says.
A Phase II trial led by Tina Cascone, M.D., Ph.D., found that adding ipilimumab to a neoadjuvant combination of nibolumab plus platinum-based chemotherapy resulted in a major pathologic response in half of all treated patients with early-stage, resectable non-small cell lung cancer. The NEOSTAR trial data, published in Nature Medicine, provided further evidence for neoadjuvant immunotherapy-based treatment to shrink tumors prior to surgery and to improve patient outcomes.
By using a novel response-adapted ultra-low dose strategy, researchers observed a 90% complete response rate in patients with orbital indolent B-cell lymphoma in a study led by Chelsea Pinnix, M.D., Ph.D., and presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting. The study was the first to prospectively examine the use of a response-adapted strategy in this setting, allowing patients to forego the higher standard doses if they had complete responses to ultra-low radiation doses.
“We are thrilled for our patients that we observed such high complete response rates when using this response-adapted strategy,” Pinnix says. “The vast majority of patients were able to avoid additional radiation doses, which minimizes potential orbital toxicity commonly associated with current standard doses.”
In Phase I data presented by Samer Srour, M.B.Ch.B., at the 2023 AACR Annual Meeting, ALLO-316, the CD70-targeting allogeneic chimeric antigen receptor (CAR) T cell therapy, demonstrated encouraging response rates and disease control rates in patients with metastatic clear cell renal cell carcinoma. The ongoing TRAVERSE trial is the first-in-human study evaluating ALLO-316 in patients who failed both checkpoint and tyrosine kinase inhibitors.
In a study published in Nature Medicine, intratumoral delivery of an engineered oncolytic virus (DNX-2401) targeting glioblastoma cells combined with subsequent immunotherapy was safe and improved survival outcomes in a subset of patients with recurrent disease. Invented by Frederick Lang, M.D., Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D., DNX-2401 is a cold virus engineered to selectively target and invade glioblastoma cells while avoiding normal ones.
“This therapeutic strategy aims to awaken the patient’s immune system and trigger a healing from within,” Fueyo says. “After injection, patients that respond well develop inflammation inside the tumor, triggering an immune response that first kills the virus. Once the virus is wiped out, the continued immune reaction, stimulated by additional immunotherapy, destroys the cancer cells in a tightly regulated way without the side effects common to chemotherapy or radiation therapy.”
To uncover the underlying mechanisms of treatment resistance and identify new therapeutic strategies, researchers led by Zhicheng Zhou, Ph.D., Mei-Ju May Chen, Ph.D., Yikai Luo, and Han Liang, Ph.D., analyzed several immune-oncology targets in patients with melanoma who received anti-PD-1 treatment. They discovered a new role for the tumor-intrinsic SIRPA gene, a known inhibitory immune regulator in macrophages, in melanoma cells. They also found that higher SIRPA expression was associated with better responses to immune checkpoint inhibitors. The findings, published in Cancer Cell, suggest the potential to improve immunotherapy responses by more specifically targeting SIRPA.
Patients across several tumor types showed encouraging responses and long-lasting clinical benefit in the Phase II DESTINY-PanTumor-02 study of trastuzumab deruxtecan, a HER2-targeted antibody drug conjugate already approved in the U.S. for HER2 positive gastric cancer and HER2-mutant lung cancer. Led by Funda Meric-Bernstam, M.D., the trial showed especially notable results in the gynecologic cancer cohorts and in patients with higher levels of HER2 expression.
“This could help provide a new treatment option for these patients with advanced disease and hard-to-treat HER2 positive cancers who currently have very limited or no options,” says Meric-Bernstam, who presented the results at the 2023 ASCO Annual Meeting.
In a study published in Nature Cancer, researchers developed a new model of aggressive renal cell carcinoma that highlighted molecular targets and genomic events that trigger chromosomal instability and drive metastatic progression. Led by Luigi Perelli, M.D., Ph.D., and Giannicola Genovese, M.D., Ph.D., researchers demonstrated that the loss of a cluster of interferon receptor genes plays a pivotal role in allowing cancer cells to become tolerant of chromosomal instability, a feature which may be used to help clinicians predict a tumor’s potential to metastasize and resist treatment.
According to data published in the Journal of Clinical Oncology, a blood-based test developed at MD Anderson combined with a personalized risk model can better predict an individual’s risk of dying from lung cancer than the current U.S. Preventive Services Task Force criteria. “This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” says Samir Hanash, M.D., Ph.D., who led the study with Edwin Ostrin, M.D., Ph.D. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach."
After uncovering a functional role for KRAS mutations in pancreatic cancer, researchers translated the findings into a novel therapeutic approach combining a KRAS G12D inhibitor with immune checkpoint inhibitors for early- and late-stage KRAS G12D-mutant pancreatic cancer. This combination therapy led to durable tumor elimination and significantly improved survival outcomes in preclinical models, which led to the launch of a Phase I trial. One study, published in Development Cell, detailed the development of new models to provide better insight into the molecular function of oncogenic KRAS. A second study published the same day in Cancer Cell built on the first by investigating the effects of the KRAS G12D inhibitor MRTX1133 in 16 different models. This collaborative effort was led by Krishnan Mahadevan, Ph.D., Kathleen McAndrews, Ph.D., Raghu Kalluri, M.D., Ph.D., Anirban Maitra, M.B.B.S., and Timothy Heffernan, Ph.D.
“These results are a testament to the value of team science and to the incredible research environment at MD Anderson, which enables the accelerated and seamless translation from genetic models to clinical application,” Kalluri says. “We are encouraged that these results could lead to meaningful benefits for patients.”