ATM (ATM serine/threonine kinase)

P2, N=130, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Suspended --> Terminated; Bankruptcy of partner: Clovis

To address this, we generated in vitro prostate cancer models of acquired PARPi resistance to olaparib and saruparib, a novel selective PARP1 inhibitor and pursued functional characterization and drug sensitivity studies. Consistently, we demonstrate in vivo that the combination of PARPi-ATRi in resistant models restores treatment sensitivity through enhancing replication stress. Collectively, these findings highlight an interplay between ATM-ATR signaling as a key mediator of PARPi sensitivity in ATM-deficient mPC and identify a promising therapeutic combination to prolong treatment response and potentially improve patients' outcomes.

Therapeutic annotation using OncoKB identified 223 actionable or likely oncogenic variants, highlighting potential targets for precision oncology. This study provides a comprehensive characterization of the breast cancer mutational landscape in MENA patients and offers a valuable resource for advancing genomic and therapeutic research in this demographic.

Using a 73-gene panel, we characterized the molecular characteristics of GISTs and revealed a correlation with their clinical features. Moreover, KIT/PDGFRA-dependent and KIT/PDGFRA-independent mechanisms underlying resistance to imatinib were explored. Overall, our 73-gene panel is sufficient for clinical application in cases of GISTs.

This optimized dosing schedule successfully established the MTD for RUB with nal-IRI and 5-FU, overcoming prior challenges with PARP inhibitor and irinotecan combinations. The promising ORR and DCR support further evaluation of this regimen in advanced GI malignancies.

In this study we report the frequency of pathogenic/likely pathogenic (P/LP) germline variants in Indian patients with NSCLC with significant family history of cancer to be 16.5%. It suggests the potential utility of genetic testing to guide targeted screening strategies in this high-risk population.

We demonstrated that ATM-mutant status is associated with longer mOS compared to ATM-WT and has higher predicted immunogenetic mutations. Our results are rather hypothesis-generating and would benefit from further validation in prospective trials.

Additionally, combining BMN673 with radiotherapy exerted a synergistic anticancer effect on ATM-deficient CRC cells, which was prevented by autophagy inhibition. The findings identified the ATF4-GDF15 pathway as a crucial mediator of BMN673 sensitivity in ATM-deficient CRC cells, revealing therapeutic vulnerability beyond canonical DNA damage repair pathways and providing new insight for combination therapy strategies.

Standard therapies include alemtuzumab-based regimens and hematopoietic stem cell transplantation, although relapse rates remain high. This case underscores the need to recognize indolent presentations of T-cell prolymphocytic leukemia that may be managed conservatively. Further research is required to identify prognostic markers and optimize therapeutic strategies.

Collectively, these key genes play a significant role in the occurrence and progression of comorbidities through the pathways mentioned above. The dysregulation of key genes (SYTL1, PARVG, ID4, IL1RN, S100A9) in the context of PCOS-EC comorbidities, along with their associated enrichment pathways, including the TGF-β signaling-pathway and immune microenvironment, plays a significant role in the occurrence and progression of EC.

Patients and their relatives have played, and continue to play, a major role in the development of oncogenetics. We owe them quality tests, information, support and protection.