The USC Norris Comprehensive Cancer Center is a cancer center owned and operated by the University of Southern California (USC) through its Keck School of Medicine. Kenneth True Norris Jr. provided the money to build the hospital after voters rejected a bond offering proposed by USC and Los Angeles County; the hospital opened in 1983.Tenet Healthcare acquired the center in 2003 and sold it, along with Keck Hospital of USC, to USC in 2009 for $275 million after three years of litigation between the parties.
Understanding performance status (PS) is an essential aspect of oncologic care. PS is traditionally evaluated using the Karnofsky Performance Status (KPS) or Eastern Cooperative Oncology Group (ECOG) performance scales. Despite their ubiquity, these tools rely on subjective clinician interpretation and broad clinical categories, which contribute to poor inter-rater reliability and imprecise patient characterization. This study explores digital approaches to PS by leveraging three-dimensional video recordings and kinematic movement data to provide more objective, granular evaluations. In this single-center observational study, 34 oncology patients performed a standardized chair-to-table (CTT) movement. Of these participants, 52.9
TPS5129 Background: Management of patients (pts) with mCSPC remains a challenge due to its incurable nature and heterogeneous response to androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI). Recent analyses of phase III ADT + ARPI trials show that mCSPC with suboptimal PSA response (≥0.2ng/ml at 6-12 months) have poor prognosis, short time to castration-resistance (CRPC) and 30-36 month median overall survival (OS). While docetaxel could also be utilized in mCSPC, there is equipoise about its use in ARPI-treated pts because of 1) an absence of randomized data for docetaxel in this setting, 2) toxicity of docetaxel with impact on quality of life for pts, and 3) selection of docetaxel treatment by disease volume rather than disease biology. CCTG-PR26 (TRIPLE-SWITCH) is a joint CCTG-SWOG trial run through the NCI National Clinical Trials Network. This study investigates whether adding docetaxel prior to development of CRPC, regardless of disease volume, will improve OS in ARPI-treated mCSPC pts that show evidence of suboptimal response. Methods: This international, open-label, randomized phase III trial compares standard ADT + ARPI against the addition of docetaxel to ADT + ARPI in mCSPC pts with suboptimal PSA response, defined as PSA ≥0.2 ng/mL after 6-12 months of ADT and ≥4 months of ARPI. Stratification will be based on PSA levels, ARPI type, presence of liver metastasis, disease recurrence status, and time since ADT initiation. Arm 1 will continue standard ADT + ARPI (abiraterone acetate with prednisone, apalutamide, enzalutamide or darolutamide). Arm 2 will receive docetaxel 75mg/m 2 IV every 3 weeks for up to 6 cycles in addition to continuing standard ADT + ARPI. Sample size is 830 pts in order to detect a targeted 33% improvement in overall survival (hazard ratio 0.75) using a 1-sided 0.025 level test with 85% power. Key eligibility criteria are: ≥18 years, histologically confirmed prostate adenocarcinoma, metastatic disease present and confirmed by conventional imaging (CT and/or bone scan), PSA ≥5.0 ng/mL prior to ADT, receipt of ADT for 6-12 months and ARPI for ≥4 months, PSA ≥0.2 ng/mL within 14 days of enrolment, adequate organ and marrow function, ECOG performance status 0-2, eligible for docetaxel chemotherapy, no evidence of disease progression or biochemical progression on ADT prior to enrolment. Primary endpoint is overall survival. Secondary endpoints include PSA response, PSA kinetics, and clinical progression free-survival. Correlative studies will explore the prognostic and predictive value of circulating tumor DNA (ctDNA) and the association between molecular signatures in primary prostate cancer tissue and clinical outcomes. Enrolment has been initiated in January 2025 and is ongoing. Clinical trial information: NCT06592924 .
Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.
MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles.
Alterations in the mitogen-activated protein kinase (MAPK) pathway play a central role in colorectal cancer (CRC) tumor biology, therapeutic response, and resistance. RAS oncogenic mutations are present in up to 35% of CRC; they represent constitutively active molecular switches that impair GTP hydrolysis and promote ligand-independent signaling. The development of allele-specific KRAS G12C inhibitors exploits a cryptic pocket to trap the protein in its inactive (OFF) conformation. In metastatic CRC, where EGFR feedback loop limits monotherapy efficacy, combinations of KRAS G12C inhibitors with EGFR blockade and chemotherapy have demonstrated meaningful activity. Parallel efforts allowed the development of RAS(ON) inhibitors that sterically block the interaction with downstream effectors. Co-occurring genomic alterations, MAPK pathway reactivation, and pharmacologic limitations drive primary and acquired resistance. BRAF V600 mutations drive approximately 10% of CRCs; first-generation, type I BRAF inhibitors require combination with upstream EGFR, downstream MEK/ERK blockade to overcome adaptive feedback reactivation. Emerging strategies include paradox breaking RAF inhibitors, type II pan-RAS inhibitors, and immunotherapy combinations, particularly relevant for the immune-activated phenotype of BRAF-mutant microsatellite stable tumors. Beyond RAS and RAF, novel therapeutic avenues (such as antibody-drug conjugates, bispecific antibodies, DNA damage response inhibitors, and tumor microenvironment modulating agents) are reshaping precision oncology in CRC. Integrating multiomics profiling with dynamic biomarkers may enable durable activity and personalized treatment strategies.
