Cancer Discov
· 2026 Jun · PMID 42299102
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A 14-protein blood test can identify people at high risk of lung cancer more than 5 years before a tumor becomes detectable on imaging, including never-smokers who fall outside current screening criteria. In a retrospect...A 14-protein blood test can identify people at high risk of lung cancer more than 5 years before a tumor becomes detectable on imaging, including never-smokers who fall outside current screening criteria. In a retrospective analysis, the test also identified individuals most likely to benefit from the anti-IL-1β drug canakinumab, which roughly halved lung cancer incidence in the high-risk group but not in low-risk participants.
Cancer Discov
· 2026 Jun · PMID 42261652
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In the phase I inMMyCAR study of the in vivo chimeric antigen receptor (CAR) T-cell therapy KLN-1010, all 18 patients with multiple myeloma responded. None of the evaluable patients had minimal residual disease 1 month a...In the phase I inMMyCAR study of the in vivo chimeric antigen receptor (CAR) T-cell therapy KLN-1010, all 18 patients with multiple myeloma responded. None of the evaluable patients had minimal residual disease 1 month after treatment, suggesting that the therapy could prove clinically useful.
Cancer Discov
· 2026 Jun · PMID 42261650
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For people with localized, high-risk prostate cancer, treatment with 6 months of apalutamide and androgen deprivation therapy (ADT) both before and after surgery reduces the risk of metastases and death compared with per...For people with localized, high-risk prostate cancer, treatment with 6 months of apalutamide and androgen deprivation therapy (ADT) both before and after surgery reduces the risk of metastases and death compared with perioperative ADT alone, according to results of the phase III PROTEUS trial. At 5 years, 78.2% of patients who received apalutamide plus ADT were alive and free from metastasis, compared with 73.5% in the ADT only group.
Ye H, McDonald TO, Elghaish R
… +13 more, Sei E, Conterno Minussi D, Hu M, Bai S, Tang C, Wang J, Wang K, Downey RJ, Casasent A, Nicholson MD, Chen H, Michor F, Navin NE
Cancer Discov
· 2026 Jun · PMID 42258702
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Aneuploidy is a hallmark of human tumors. While patient-level copy number alteration (CNA) differences have been investigated extensively in large cohorts, their intratumoral heterogeneity remains understudied. Here, we...Aneuploidy is a hallmark of human tumors. While patient-level copy number alteration (CNA) differences have been investigated extensively in large cohorts, their intratumoral heterogeneity remains understudied. Here, we conducted a pan-cancer analysis of 94 human tumors at single cell resolution, representing seven cancer types: bladder, breast, colon, glioblastoma, kidney, lung, and ovarian. Single-cell copy number profiling was used to analyze 62,646 aneuploid cells, in addition to bulk exome sequencing of most patients and single-nucleus RNA-seq of 6 samples. In many cancer types, increased subclonal diversity was associated with higher CNA burden, whole genome doubling, TP53 mutations, and increased geographic diversity. Cancer cells from each patient shared a set of truncal CNAs, suggesting evolution from a single ancestral cell. Many tumors accumulated CNAs in bursts of evolution, suggesting that punctuated evolution is common in diverse cancer types. This study greatly improves our knowledge of intratumoral chromosome diversity across human cancers.
Cancer Discov
· 2026 Jun · PMID 42249527
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The treatment arsenal for small cell lung cancer could soon include antibody-drug conjugates, with early data from three phase I studies indicating robust response rates to CD56-targeting DXC006, DLL-3-targeting BL-M14D1...The treatment arsenal for small cell lung cancer could soon include antibody-drug conjugates, with early data from three phase I studies indicating robust response rates to CD56-targeting DXC006, DLL-3-targeting BL-M14D1, and B7-H3-targeting SYS6043. The latter also appears active in other tumor types, including ovarian and breast cancers. As well, phase II findings on a fourth ADC candidate, HER2-targeting trastuzumab brengitecan, suggest its strong efficacy in platinum-resistant ovarian cancer.
Liu W, Wang X, Zhang Y
… +20 more, Liu J, Li M, Zhou Q, Wang L, Liu S, Chen W, Chu ES, Lau HC, Song Q, Zhou X, Gou H, Zhang JX, Tian GB, Wang L, Li X, Peng S, Wong CC, Kuang M, Xu L, Yu J
Cancer Discov
· 2026 Jun · PMID 42240277
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The role of intrahepatic microbiome in hepatocellular carcinoma (HCC) remains elusive. Here, we profiled matched gut and intrahepatic microbiomes from HCC patients and healthy subjects. Compared to healthy subjects, we o...The role of intrahepatic microbiome in hepatocellular carcinoma (HCC) remains elusive. Here, we profiled matched gut and intrahepatic microbiomes from HCC patients and healthy subjects. Compared to healthy subjects, we observed increased gut-liver microbiome similarity and a gut pathobionts-centred network in HCC, implying microbial transfer via gut-liver axis. Consistently, HCC stool transplantation to germ-free mice impaired gut barrier function and increased bacterial load in liver. Multi-site analysis of intrahepatic microbiome and host transcriptome revealed that gut pathobionts in tumor regions positively correlate with host cytokine expression and oncogenic pathways. Administration of HCC-enriched Bacteroides fragilis disrupted gut barrier in mice and led to live bacteria translocation to liver. Bacteroides fragilis exacerbated liver damage and promoted HCC development in mice. Mechanistically, Bacteroides fragilis surface protein Enolase interacts with and activates Vimentin on hepatocytes, triggering oncogenic cascades. Our findings provide insight into how gut pathobionts translocate to liver to promote hepatocarcinogenesis.
The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy...The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy is potentially IOS-1002, an antagonist of two immunosuppressive receptors, LILRB1/2 and KIR3DL1, combined with anti-PD-1 pembrolizumab. As well, an update on the recently published DART (NCI/SWOG S1609) study indicates that the classic combination of ipilimumab with nivolumab may benefit even more rare cancers, including gestational trophoblastic neoplasia.
The anti-PD-1, anti-VEGF bispecific antibody ivonescimab plus chemotherapy significantly improves overall survival in advanced squamous non-small cell lung cancer versus an immunotherapy-chemotherapy combination, accordi...The anti-PD-1, anti-VEGF bispecific antibody ivonescimab plus chemotherapy significantly improves overall survival in advanced squamous non-small cell lung cancer versus an immunotherapy-chemotherapy combination, according to a trial conducted in China. However, questions remain over the trial's applicability to patients in other countries.
Results from LIBRETTO-432 demonstrate that adjuvant selpercatinib yields a substantial improvement in event-free survival for patients with early-stage RET fusion-positive non-small cell lung cancer. Experts say the find...Results from LIBRETTO-432 demonstrate that adjuvant selpercatinib yields a substantial improvement in event-free survival for patients with early-stage RET fusion-positive non-small cell lung cancer. Experts say the findings establish selpercatinib as a new standard of care for this rare disease, although questions remain over identifying patients and access to screening.
The pan-RAS inhibitor daraxonrasib led to an unprecedented doubling of overall survival compared with chemotherapy for patients with pancreatic ductal adenocarcinoma in a phase III study. The data, presented at the Ameri...The pan-RAS inhibitor daraxonrasib led to an unprecedented doubling of overall survival compared with chemotherapy for patients with pancreatic ductal adenocarcinoma in a phase III study. The data, presented at the American Society of Clinical Oncology Annual Meeting, cement the drug as a new standard-of-care for the second-line treatment for metastatic disease and motivate further trials of RAS-targeted therapies.
Findings from the phase III WU-KONG28 trial indicate that the next-generation tyrosine kinase inhibitor sunvozertinib, an approved later-line option for patients with non-small cell lung cancer harboring EGFR exon 20 ins...Findings from the phase III WU-KONG28 trial indicate that the next-generation tyrosine kinase inhibitor sunvozertinib, an approved later-line option for patients with non-small cell lung cancer harboring EGFR exon 20 insertions, also looks effective up front, besting chemotherapy. Meanwhile, updated CHRYSALIS-2 data point to amivantamab combined with lazertinib as a new option for patients with atypical EGFR mutations, with initial efficacy translating to durable overall survival.
Cercek A, Zabransky DJ, Mauri G
… +3 more, Jaffee EM, Bardelli A, Rebbeck TR
Cancer Discov
· 2026 Jun · PMID 42220010
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Early-onset cancers are increasing globally, yet traditional research frameworks have yet to inform the epidemiologic and biological underpinnings of this trend. This perspective summarizes the current state of knowledge...Early-onset cancers are increasing globally, yet traditional research frameworks have yet to inform the epidemiologic and biological underpinnings of this trend. This perspective summarizes the current state of knowledge and prospects for a research agenda spanning epidemiology, exposure science, mechanistic studies, and federated infrastructures to address this emerging challenge.
Cancer Discov
· 2026 Jun · PMID 42220009
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Glioblastoma (GBM) cells secrete C1QL1, which binds BAI3 on nearby neurons and tumor cells to activate RAC1, promoting tumor microtube growth, malignant synapse formation, and remodeling of normal synapses. Blocking RAC1...Glioblastoma (GBM) cells secrete C1QL1, which binds BAI3 on nearby neurons and tumor cells to activate RAC1, promoting tumor microtube growth, malignant synapse formation, and remodeling of normal synapses. Blocking RAC1 with a targeted inhibitor disrupts this process and may help prevent GBM recurrence. See related article by Ding et al., p. 1176.
Cancer Discov
· 2026 Jun · PMID 42220008
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First-generation RAS inhibitory drugs have failed to live up to expectations in the clinic, but a preclinical study of a combination of two ON-state RAS inhibitors, one mutant-selective and one targeting all RAS forms, s...First-generation RAS inhibitory drugs have failed to live up to expectations in the clinic, but a preclinical study of a combination of two ON-state RAS inhibitors, one mutant-selective and one targeting all RAS forms, shows greatly reduced development of drug resistance. Most strikingly, this RAS inhibitor doublet combines very effectively with immune checkpoint blockade, leading to complete immune elimination of even highly refractory cancers with immune-cold tumor microenvironments, generating hope for real progress in tackling RAS-mutant tumors in the clinic. See related article by Wei et al., p. 1152.
Cancer Discov
· 2026 Jun · PMID 42220007
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Using integrated multiomic and spatially resolved single-cell profiling of high-grade serous ovarian cancer, Perez-Villatoro and colleagues show that tumor cell-intrinsic MHC class II (MHCII) expression and the organizat...Using integrated multiomic and spatially resolved single-cell profiling of high-grade serous ovarian cancer, Perez-Villatoro and colleagues show that tumor cell-intrinsic MHC class II (MHCII) expression and the organization of tumor-stroma interface niches are major determinants of endogenous antitumor immune activity and clinical outcome. These data argue against models based solely on bulk immune infiltration and instead support a context-dependent framework in which tumor cell state (particularly MHCII expression), spatial immune topology, and prior therapeutic exposure collectively shape the magnitude and quality of immune pressure during disease evolution. See related article by Perez-Villatoro et al., p. 1100.
Data unveiled at this year's ASCO Annual meeting show that GRAIL's Galleri multi-cancer early detection (MCED) test failed to reduce stage III and IV cancers in the landmark NHS-Galleri trial, although there was an impro...Data unveiled at this year's ASCO Annual meeting show that GRAIL's Galleri multi-cancer early detection (MCED) test failed to reduce stage III and IV cancers in the landmark NHS-Galleri trial, although there was an improvement in stage IV alone. Experts say the findings fall short of demonstrating a large enough clinical benefit for MCED testing that would warrant Galleri's implementation.