MYC amplification

P=N/A, N=38, Recruiting, Assiut University

These findings suggest that distinct oncogenic mechanisms contribute to differential sensitivity to chemotherapy in younger and elderly patients. Cancer genome profiling may aid in chemotherapy selection, and its early implementation is recommended to optimize treatment strategies.

We developed paclitaxel-, doxorubicin-, and cisplatin-resistant MDA-MB-231 cells to study MYC's role in upregulating DNA repair genes during drug resistance development...The combined use of asiRNA-VP (Vinylphosphonate) with dacomitinib or talazoparib was synthetic lethal in TNBC cell lines...We confirmed that MYC knockdown upregulated cFLIP, BCL2, STAT1, pSTAT1, STAT2, and cleaved saspase-3 in both TNBC and non-small cell lung cancer (NSCLC) cell lines. Finally, we recommend a combination treatment approach that synergizes with MYC inhibition rather than monotherapy or indirect targeting via upstream regulators such as the BRD4 and RRM2 genes or selective modulation at the protein level to suppress anti-apoptotic genes (cFLIP and BCL2) at the same time.

MYC amplification was reported to be a main contributor to the development of resistance. Six trials are currently ongoing, including one randomized trial, and promising results are expected from combination with other agents, such as immune-checkpoint blockers.

We also performed methylation classification using nanopore-based methylation data to successfully categorize the tumor as AS. This case report highlights the potential utility of nanopore sequencing in the diagnosis of sarcomas.

P1, N=110, Completed, Vincerx Pharma, Inc. | Active, not recruiting --> Completed

Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.

Together, our data suggest that ancestry may influence amplification of not only MYC but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-MYC therapeutic approaches.

Furthermore, targeting KLRG1 alone or combined with MYC inhibition using an eIF4 inhibitor is effective against NK-cell tumors. Therefore, our observations provide insights into the pathogenesis and highlight potential therapeutic targets, including CXCL16, KLRG1, and MYC, in ENKTCL, which can help improve its diagnostic and therapeutic strategies.

Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.

Gemcitabine and nab-paclitaxel demonstrated similar clinical activity and toxicity compared to previous retrospective reports utilizing gemcitabine and docetaxel in patients with recurrent osteosarcoma. Serial analysis of CTC and ctDNA was feasible in this prospective multi-institution study and provides preliminary data on the use of these assays in patients with relapsed disease.

Compared to HSCDA Proficient mice, tumors from HSCDA Deficient mice showed reduced densities of dendritic cells (DC) and natural killer (NK) cells, as well as fewer DCs, NKs, and B-cells in proximity to tumor cells, as determined by spatial analysis. Overall, our data suggest that HSCDAs promote HGSC survival and plasticity while downregulating expression of tumor suppressors and altering the peritoneal immune and metabolic environment to promote HGSC progression.