TP53 deletion

P1, N=32, Not yet recruiting, Northside Hospital, Inc.

However, a subset of aged mice with mutated Rps15 eventually develop B-cell leukemia (37% penetrance), which exhibits increased Myc activity with strong pro-survival and proliferation signatures. Mutant RPS15 thus induces both hypo- and hyper-proliferative signals, initially weighted towards cell cycle arrest; and that through translational rewiring, oxidative stress, DNA damage response defects and genomic instability set the stage for the acquisition of additional driving mutations, such as TP53 deletion, that can overcome this cell cycle block to trigger tumorigenesis.

The median overall survival of 5 patients with available follow-up was 11 months. We conclude that the reciprocal translocation t(5;12)(q32;p13) requires a careful and step-wise diagnostic work-up to differentiate between an underlying ETV6::PDGFRB fusion gene with associated excellent prognosis on imatinib and an ETV6::ACSL6 fusion gene, for which the prognosis is poor and alloHCT appears to be a promising therapeutic option.

Subsequent bioinformatics analysis identified 8 core targets involved in TQ's anti-OS activity. Enrichment analysis indicated that these core targets modulate a range of biological processes and may influence multiple molecular pathways.ResultsPreliminary in vitro data indicated that TQ effectively reduces OS cell proliferation, induces apoptosis, and downregulates the expression of P53 and HMOX1 proteins.ConclusionOur findings elucidate the molecular mechanisms underlying TQ's effectiveness against OS, highlighting potential apoptosis-related therapeutic targets, such as P53 and CYCLIN D1, for the treatment of OS with TQ.

P1/2, N=62, Not yet recruiting, Natalie Callander

Oxaliplatin (OXA) is combined with the fluoropyrimidine (FP) drug 5-fluorouracil (5-FU) in the FOLFOX regimen used to treat advanced colorectal cancer (CRC)... Our results demonstrate that OXA synergizes with CF10 more effectively than with 5-FU through enhanced replication stress in both WT and TP53-null cells by causing greater Top1-mediated DNA double-strand breaks. Our studies provide a foundation for further testing of this combination in an orthotopic liver metastatic setting and eventual clinical development.

P2, N=235, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Mar 2026; <75% participation

Among patients receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction therapy, those with cytogenetic abnormalities showed significantly lower deep response rates (complete response + very good partial response). Furthermore, RB1 deletion or D13S319 deletion combined with other high-risk indicators further shortened PFS. These findings indicate that integrating expanded cytogenetic markers optimises MM risk stratification and provides a basis for individualised treatment strategies.

Collectively, these findings highlight Fgfr3+ endosteal stem cells as candidate cells of origin for osteosarcoma and underscore the dual role of SSC-derived lineages in both tumor initiation and progression. Targeting SSC-derived endosteal niches may provide new therapeutic opportunities for bone malignancies.

Here, we report a case of an ALK-positive lung adenocarcinoma patient who developed resistance following sequential treatment with the ALK-TKI alectinib and lorlatinib, accompanied by histological transformation to LCNEC and concurrent genetic alterations including TP53 deletion, CDKN2A deletion, and MYC amplification. This case expands the spectrum of ALK-TKI resistance mechanisms and highlights the potential value of exploring combinatorial approaches incorporating immunotherapy, antiangiogenic therapy, and chemotherapy for the management of such cases.

An improved diagnostic algorithm based on the combined use of FISH and NGS methods makes it possible to increase the accuracy of identification of genetic subtypes of aggressive B-cell lymphomas in children. This helps to categorize the diagnosis based on the molecular and genetic characteristics of the tumor, paving the way for improved prognosis and treatment effectiveness.

These data demonstrate the role of PDLIM2 in suppressing lung adenocarcinoma metastasis, thereby improving our understanding of this crucial tumor suppressor and lung cancer. They also provide a useful model for studying metastasis and testing new lung cancer treatments in vivo .