MSI-like GES does not identify a population with higher sensitivity to immune checkpoint plus angiogenesis inhibition. However, responses are promising in patients with MSI tumors and, to a lesser extent, in patients without liver metastasis regardless of MSI status.

P2, N=236, Not yet recruiting, Sun Yat-sen University

P2, N=38, Completed, Asan Medical Center | Unknown status --> Completed

P2, N=35, Not yet recruiting, Sun Yat-sen University

P2, N=105, Not yet recruiting, BioNTech SE

P=N/A, N=572, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Subsequently, multiple hepatic metastases and pelvic dissemination developed, and conventional chemotherapy including bevacizumab was ineffective...Switching to sorafenib led to further progression, but reintroduction of LVB reduced Tg levels...The patient has survived seven years since recurrence, including six years on LVB. The tumor behaved similarly to poorly differentiated thyroid carcinoma, with Tg levels reflecting disease activity and LVB demonstrating the potential for long-term tumor control.

These subtypes showed distinct tumor cell-intrinsic and extrinsic features, including different immune contextures, and importantly an association with clinical response to atezolizumab plus bevacizumab combination immunotherapy. In a humanized HCC xenograft mouse model recapitulating the GPC3-high progenitor-like subtype, a GPC3/CD3 bispecific antibody elicited strong antitumor activity mediated by intratumoral recruitment and activation of T cells. Our study provides biological insights into HCC heterogeneity and potential strategies for targeting subtype-specific vulnerabilities.

Immunophenotyping demonstrated TTF-1 nuclear positivity in the metastatic tumor alongside a classic colorectal profile: cytokeratin 7 (CK7) negativity, cytokeratin 20 (CK20) positivity, strong caudal-type homeobox transcription factor 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) nuclear expression, and absence of Napsin A. The patient underwent surgical resection of the primary sigmoid colon tumor and received 16 cycles of capecitabine plus bevacizumab chemotherapy. We discuss how the comprehensive immunohistochemical panel and genetic findings confirmed the colorectal origin of the lung lesions, emphasizing that combined marker profiles (TTF-1 +/CK7 -/CK20 +/CDX2 +/SATB2 +/Napsin A -) are more consistent with metastatic colorectal adenocarcinoma rather than an enteric-type adenocarcinoma of the lung, primary. The report reviews relevant literature and underscores the importance of correlating clinical history with pathology to avoid misdiagnosis.

The Atezolizumab-Bevacizumab-Cluster (A-B-C) classification for unresectable HCC identified subgroups with histology, hepatic decompensation and patterns of progression, and prognostic trajectories, informing hypothesis generation for trial design and patient selection.

Maximal safe resection followed by chemoradiotherapy with temozolomide remains the standard, with the greatest benefit seen in O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. Bevacizumab and other targeted modalities offer mainly progression-free, not overall survival, gains. Immune checkpoint inhibitors (e.g., nivolumab) have not improved survival in unselected GBM, while early multi-antigen CAR-T (chimeric antigen receptor T-cell) strategies show preliminary bioactivity without established durability...Future priorities include harmonized imaging molecular integration, AI-driven prognostic modeling, novel PET tracers, and strategies to breach or transiently open the blood-brain barrier to enhance drug delivery. Convergence of these domains may convert diagnostic precision into improved patient outcomes.

P3, N=621, Recruiting, BioNTech SE | Active, not recruiting --> Recruiting | N=439 --> 621 | Trial completion date: Sep 2028 --> Mar 2029 | Trial primary completion date: Apr 2028 --> Dec 2028