Elacestrant plus alpelisib in an and co-mutated and heavily pretreated metastatic breast cancer: the first case report for combination efficacy and safety.

Breast cancer (BC) is the leading cause of cancer-related mortality among women, and hormone receptor (HR)-positive subtype makes up the majority of all cases. The standard of care in HR/HER2 metastatic BC (MBC) is endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i). mutations could impair the clinical efficacy of the ETs.

Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors.

Background: Kinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class III BRAF variants differ from class I and class II mutations in terms of mechanism of pathway activation and therapeutic vulnerabilities. Genomic landscape analyses of tumors in large real-world cohorts represent a great opportunity to further characterize tumor-related molecular events and treatment vulnerabilities, however, such data is not yet available for tumors with BRAF class III mutations.

Alterations of ceramide synthesis induce PD-L1 internalization and signaling to regulate tumor metastasis and immunotherapy response.

Programmed death ligand 1, PD-L1 (CD274), facilitates immune evasion and exerts pro-survival functions in cancer cells. Here, we report a mechanism whereby internalization of PD-L1 in response to alterations of bioactive lipid/ceramide metabolism by ceramide synthase 4 (CerS4) induces sonic hedgehog (Shh) and transforming growth factor β receptor signaling to enhance tumor metastasis in triple-negative breast cancers (TNBCs), exhibiting immunotherapy resistance. Mechanistically, data showed that internalized PD-L1 interacts with an RNA-binding protein, caprin-1, to stabilize Shh/TGFBR1/Wnt mRNAs to induce β-catenin signaling and TNBC growth/metastasis, consistent with increased infiltration of FoxP3 regulatory T cells and resistance to immunotherapy.

Case report: Precision guided reactive cancer management: molecular complete response in heavily pretreated metastatic CRC by dual immunotherapy and sorafenib.

Background: Metastatic colon adenocarcinoma presents significant challenges in treatment, particularly when resistant to standard therapies. Precision oncology, guided by multidisciplinary tumor boards (MTBs), offers a promising way for individualized therapeutic approaches. Integration of comprehensive genomic profiling (CGP) and minimal residual disease (MRD) testing strengthens treatment decision-making, yet challenges persist in identifying and overcoming resistance mechanisms.

Durable radiologic and molecular complete response following nivolumab in an HNSCC patient with UV signature and HIV.

Cancer patients living with HIV (CPLWH) may experience increased mortality risk. Furthermore, they have been historically excluded from clinical trials due to safety concerns. Our patient with squamous cell carcinoma of the lower lip received radiotherapy and platinum-based chemotherapy but declined by multiple centers due to his accidental HIV status.

Navigating uncharted territory: a case report and literature review on the remarkable response to personalized crizotinib containing combinational therapy in a pazopanib refractory patient with novel alterations.

This paper presents a patient with a novel Ig-like-III domain fibroblast growth factor receptor (FGFR2) alteration (W290_P307>C) along with CDKN2A/B alterations and a cadherin 1 (CDH1) alteration. Initial responsiveness to pazopanib monotherapy was encouraging, yet progression occurred after 7.5 months.

Targeting LINC00152 activates cAMP/Ca/ferroptosis axis and overcomes tamoxifen resistance in ER+ breast cancer.

Tamoxifen has been the mainstay therapy to treat early, locally advanced, and metastatic estrogen receptor-positive (ER+) breast cancer, constituting around 75% of all cases. However, emergence of resistance is common, necessitating the identification of novel therapeutic targets. Here, we demonstrated that long-noncoding RNA LINC00152 confers tamoxifen resistance via blocking tamoxifen-induced ferroptosis, an iron-mediated cell death.

Exceptional Response to MEK Inhibition in a Patient With RAF1-Mutant Myxofibrosarcoma: Case Report and Mechanistic Overview.

Complete response to Trametinib in a heavily-pretreated sarcoma: RAF1 as a predictor of MEKi Response

PARP inhibitor combinations with high-dose vitamin C in the treatment of Ewing sarcoma: two case reports and mechanistic overview.

Ewing's sarcoma (ES) is a bone and soft tissue tumor that mainly occurs at a young age. The underlying cause of Ewing's sarcoma is the formation of fusion proteins between family genes and family genes. Tumors with fusion genes can have defects in the DNA damage response and are sensitive to PARP inhibitors (PARPi).

Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer.

Resistance to endocrine therapy and CDK4/6 inhibitors, the standard of care (SOC) in estrogen receptor-positive (ER+) breast cancer, greatly reduces patient survival. Therefore, elucidating the mechanisms of sensitivity and resistance to SOC therapy and identifying actionable targets are urgently needed. Here, we show that SOC therapy causes DNA damage and toxic PARP1 trapping upon generation of a functional BRCAness (i.

Evaluation of the Relationship between Aromatase/Sirtuin1 Interaction and miRNA Expression in Human Neuroblastoma Cells.

Background: Changes in activation/inhibition of Sirtuin-1 (SIRT1) and aromatase play an important role in a plethora of diseases. MicroRNAs (miRNAs) modulate multiple molecular pathways and affect a substantial number of physiological and pathological processes.

Objective: The aim of this study was to investigate any possible interaction between aromatase and SIRT1 in SH-SY5Y cells and to see how there is a connection between this interaction and miRNA expression, if there is an interaction.

Targeting HIF1-alpha/miR-326/ITGA5 axis potentiates chemotherapy response in triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that is frequently treated with chemotherapy. However, many patients exhibit either de novo chemoresistance or ultimately develop resistance to chemotherapy, leading to significantly high mortality rates. Therefore, increasing the efficacy of chemotherapy has potential to improve patient outcomes.

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy.