Solid tumors: latest on treaments and research pathways

To discover the pathway cancer cells use to infiltrate the brain, researchers used large-scale gene editing technology to compare gene dependencies in glioblastoma when it was initially diagnosed and after it returned following standard treatments. By doing this, researchers discovered a new pathway used for axonal guidance – a signaling axis that helps establish normal brain architecture – that can become overrun by cancer cells.

The study finds that using Tumor Treating Fields therapy (TTFields), which delivers targeted waves of electric fields directly into tumors to stop their growth and signal the body's immune system to attack cancerous tumor cells, may extend survival among patients with glioblastoma, when combined with immunotherapy (pembrolizumab) and chemotherapy (temozolomide).

This systematic review and meta-analysis examined the impact of pituitary stalk sacrifice during craniopharyngioma surgery. It found that sacrificing the stalk significantly increases the risk of postoperative endocrine dysfunction without reducing tumor recurrence or progression, highlighting the importance of preserving the stalk when possible.

CAR-T activity is still modest in GBM, and there are multiple limitations to its use in this setting, said Elena Garralda, MD, PhD, of Vall d'Hebron Institute of Oncology in Barcelona, who served as ASCO session study discussant.

Characterization of GBM cells has contributed to identify several molecules as targets for immunotherapy-based treatments such as EGFR/EGFRvIII, IL13Rα2, B7-H3, and CSPG4. Cytotoxic T lymphocytes collected from a patient can be genetically modified to express a chimeric antigen receptor (CAR) specific for an identified tumor antigen (TA). These CAR T cells can then be re-administered to the patient to identify and eliminate cancer cells. The impressive clinical responses to TA-specific CAR T cell-based therapies in patients with hematological malignancies have generated a lot of interest in the application of this strategy with solid tumors including GBM.

In a study published in May in Cell Death and Disease, researchers identified a previously unknown trait of cancer cells that shows promise for therapeutic intervention. The group outlined the mechanism of action and effectiveness of the experimental drug known as JM2, revealing its potential as a peptide therapy to target cancer cells that can renew and regrow, even after chemotherapy and radiation.

In the relentless fight against glioblastoma, the most common and lethal form of primary brain cancer, new research is shedding light on a previously hidden collaborator within the tumor microenvironment—astrocytes. These star-shaped glial cells, traditionally known for their supportive roles in the central nervous system, have now been implicated in actively orchestrating immune evasion strategies that allow glioblastomas to thrive despite aggressive treatments. Groundbreaking work led by Faust Akl and colleagues unravels a complex molecular dialogue where tumor-derived signals reprogram astrocytes into suppressors of anti-tumor immunity, revealing promising therapeutic avenues that could reshape glioblastoma treatment paradigms.

Our study investigated the role of astrocytes, an abundant cell type in the brain, in regulating an immune response against glioblastoma (GBM)-a highly aggressive brain cancer. We found a subset of astrocytes that limits the immune response and can be targeted with therapeutics.

In a groundbreaking study poised to shift the paradigm of glioblastoma treatment, researchers have unveiled compelling evidence that gabapentinoids, a class of drugs traditionally employed in neuropathic pain and seizure management, confer a significant survival advantage in human glioblastoma patients. This revelation arises from an extensive, multifaceted investigation that meticulously combines clinical data, molecular biology, and pharmacological insights, potentially opening new therapeutic avenues for one of the deadliest brain cancers known to medicine.

In the relentless battle against gliomas, a notoriously aggressive and often deadly form of brain cancer, the quest for effective immunotherapy targets remains a paramount scientific challenge. Gliomas’ ability to evade immune detection has historically hindered the development of T-cell mediated therapies, largely due to the scarcity of identified tumor-specific antigens that effectively trigger immune responses. However, an innovative study is poised to change this narrative by unveiling a new reservoir of potential immunogenic targets derived from the aberrant transcriptomic landscape of glioma cells. This breakthrough work not only broadens our understanding of tumor antigenicity but also illuminates a promising avenue toward personalized immunotherapies.

The phase 2B SURVIVE trial testing SurVaxM, a cancer vaccine for glioblastoma, will continue as planned following an interim analysis showing sufficient promise to proceed. SurVaxM, combined with standard treatments like surgery, radiation, and chemotherapy, aims to extend survival and improve quality of life for patients with this aggressive brain cancer.
The vaccine targets survivin, a protein that helps tumor cells evade death, and has shown a strong safety profile and encouraging survival rates in earlier studies. While specific results remain confidential due to trial regulations, the decision to continue marks a hopeful step in the development of more effective glioblastoma therapies.

In a groundbreaking advancement that promises to reshape the landscape of glioblastoma research and treatment, a team of researchers led by Yu, Basu, Baquer, and their colleagues have unveiled a novel investigative approach utilizing needle core biopsies to enable comprehensive multimodal deep-data generation. 

GSK is licensing an ABL Bio technology that yields bispecific antibodies engineered to leverage a certain transmembrane receptor to cross the blood-brain barrier to treat neurodegeneration. GSK is already partnered with Alector, which has monoclonal antibodies in clinical development for Alzheimer’s disease.

In a Phase I clinical trial reported in Nature Communications, two researchers from UT Southwestern and their colleagues showed this strategy was safe and effective. The team worked with 21 patients at medical centers, including UTSW, who had recurrent glioblastoma. They were divided into six groups, each of which received a different dose of radiation-emitting nanoparticles through CED. Patients who received the highest doses had tolerable side effects and lived an average of 17 more months after treatment, significantly longer than expected for patients with recurrent glioblastoma. The authors suggest this strategy shows promise for improving treatments for these patients.

As recently reported in Neuro-Oncology, a team led by John Liu at the University of California, San Francisco Brain Tumor Center has developed a CRISPR–Cas9-based epigenetic editing approach that sensitizes glioblastoma cells to standard chemotherapy drugs. This technology could improve the treatment of tumours that have developed resistance to these drugs.

Researchers are continuously on the lookout for innovative treatment strategies for glioblastoma, a notoriously aggressive brain cancer. Recently, an exciting preclinical study published in the esteemed journal Oncotarget explored the combination of imipridones—specifically, ONC201 and its analog ONC206—with traditional therapies like radiation (RT) and temozolomide (TMZ). The research team, led by Brown University’s Lanlan Zhou under the guidance of Wafik S. El-Deiry, focuses on a revolutionary treatment regimen termed IRT—imipridones, radiation, and temozolomide. This therapy has demonstrated a potential breakthrough in reducing tumor burden and prolonging survival in an orthotopic IDH-WT glioblastoma mouse model.

A new research paper was published in Oncotarget, Volume 16, on March 27, 2025, titled "Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT."

Using the proliferation–diffusion model to classify tumors, we identified moderately diffuse tumors with methylated MGMT status as a subgroup with significant survival benefits from SUPR. Our findings also emphasize the need for standardized definitions of tumor invasiveness cutoffs and the limitations of current imaging modalities in accurately estimating tumor cell density.

Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood–brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months.

Researchers from the University of Texas Health Science Center at San Antonio have developed a drug that more than doubled median survival time and progression-free time for patients with glioblastoma during a clinical trial. Patients who received the drug Rhenium Obisbemeda, or 186RNL, also experienced no dose-limiting toxic effects, according to a March 7 news release from UT Health San Antonio.

Recent research has spotlighted ataxin 3 (ATXN3) as a key player in eleviating glioblastoma (GBM) malignancy by promoting epithelial-mesenchymal transition (EMT). The aggressive nature of GBM—the most common and lethal primary brain tumor—poses significant treatment challenges, as reflected by high rates of recurrence and patient mortality. Findings published on March 6, 2025, reveal ATXN3's role as a deubiquitinase for ZEB1, enhancing cell invasion and migration, offering promising insights for therapeutic strategies.

Intraoperative Raman spectroscopy uses near-infrared laser light to gain molecular information without causing damage. It can be used in vivo or ex vivo without exogenous contrast agents. Clinically, the technique was primarily used with machine learning for in situ tumor detection with fiberoptics probes analyzing tissue at sub-millimeter scales one point at the time. Here we report the development of a whole-specimen spectroscopic imaging system designed to detect cancer cells at the margins of surgical specimens.

UCLA scientists have identified a potential new strategy for treating glioblastoma, the deadliest form of brain cancer, by reprogramming aggressive cancer cells into harmless ones.

Craniopharyngioma is an uncommon, slow-growing brain tumor that can occur in children or adults. Though there are two types of craniopharyngioma; children with craniopharyngioma almost always have the adamantinomatous (ACP) subtype. These tumors usually have some areas that are solid and some areas that are cystic (made up of pockets of trapped fluid).

Drug screening based on genetic changes in disease revealed that (S)-amlodipine besylate could shrink tumors in the mouse models and in a patient-derived xenograft mouse model. The therapeutic effects were associated with dampened calcium transients implicated in neuron-tumor cell interactions and with neuroendocrine neuronal activity. Together, the results illuminate tumor biology and suggest new avenues for therapy development.