Background: NCI-MATCH is a precision medicine basket trial designed to test the effectiveness of treating cancers based on specific genetic changes in patients' tumors, regardless of cancer type. Multiple subprotocols have each tested different targeted therapies matched to specific genetic aberrations. Most subprotocols exhibited low rates of tumor shrinkage as evaluated across all tumor types enrolled. We hypothesized that these results may arise because these precision cancer therapies have tumor type-specific efficacy, as is common among other cancer therapies.
Methods: To test the hypothesis that certain tumor types are more sensitive to specific therapies than other tumor types, we applied permutation testing to tumor volume change and progression-free survival data from ten published NCI-MATCH subprotocols (together n=435 patients). False discovery rate was controlled by the Benjamini-Hochberg procedure.
Results: Six of ten subprotocols exhibited statistically significant evidence of tumor-specific drug sensitivity, four of which were previously considered negative based on response rate across all tumors. This signal-finding analysis highlights potential uses of FGFR tyrosine kinase inhibition in urothelial carcinomas with actionable aberrations, MEK inhibition in lung cancers with non- mutations, and MEK inhibition in cholangiocarcinomas with mutations.
Conclusions: These findings support the value of basket trials because even when precision medicines do not have tumor-agnostic activity, basket trials can identify tumor-specific activity for future study.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081392 | PMC |
| http://dx.doi.org/10.1101/2023.03.30.23287951 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NRG1 Fusions: The New Kid on the Block.
Curr Oncol Rep
January 2025
Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC, 20007, USA.
Purpose Of Review: Neuregulin 1 (NRG1) fusions are rare but actionable oncogenic drivers that occur in a variety of tumor types, including non-small cell lung cancer (NSCLC). These fusions lead to pathophysiologic activation of HER signaling pathways, promoting tumor growth, invasion, and metastasis. Current evidence suggests that NRG1 fusion-positive NSCLC does not respond well to conventional treatments such as immunotherapy and chemotherapy.
View Article and Find Full Text PDFTumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.
Arch Pharm Res
January 2025
College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea.
Tumor microenvironment (TME) is composed of diverse cell types whose interactions, both direct and indirect, significantly influence tumorigenesis and therapeutic outcomes. Within TME, reactive oxygen species (ROS) are produced by various cells and exhibit a dual role: moderate ROS levels promote tumor initiation and progression, whereas excessive levels induce cancer cell death, influencing the efficacy of anticancer therapies. Inflammasomes, cytosolic multiprotein complexes, are pivotal in multiple stages of tumorigenesis and play a crucial role in establishing the inflammatory TME.
View Article and Find Full Text PDFBeyond checkpoint inhibitors: the three generations of immunotherapy.
Clin Exp Med
January 2025
LSU-LCMC Cancer Center, LSU School of Medicine, 1700 Tulane Avenue, Room 510, New Orleans, LA, 70112, USA.
Anti-tumor immunotherapy was rediscovered and rejuvenated in the last two decades with the discovery of CTLA-4, PD-1 and PD-L1 and the roles in inhibiting immune function and tumor evasion of anti-tumor immune response. Following the approval of the first checkpoint inhibitor ipilimumab against CTLA-4 in melanoma in 2011, there has been a rapid development of tumor immunotherapy. Furthermore, additional positive and negative molecules among the T-cell regulatory systems have been identified that that function to fine tune the stimulatory or inhibitory immune cells and modulate their functions (checkpoint modulators).
View Article and Find Full Text PDFIndividual management and prognostic assessment for long-term outcomes using a novel classification system of craniopharyngiomas: a retrospective study of single institution.
J Cancer Res Clin Oncol
January 2025
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Purpose: This study aims to propose a classification system to more accurately understand the features and nature of different CPs, to investigate the correlation between different topographies of CPs and their surgical outcomes.
Methods: A retrospective analysis was conducted on 91 surgically resected CPs. They were categorized into six types based on their location and origin.
The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.
Adv Sci (Weinh)
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Zhongshan Hospital Immunotherapy Translational Research Center, Fudan University, Shanghai, 200032, China.
BTB domain and CNC homolog 1 (BACH1) belongs to the family of basic leucine zipper proteins and is expressed in most mammalian tissues. It can regulate its own expression and play a role in transcriptionally activating or inhibiting downstream target genes. It has a crucial role in various biological processes, such as oxidative stress, cell cycle, heme homeostasis, and immune regulation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!