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CANCER:

Merkel Cell Carcinoma

Related cancers:
21h
Analyses of tertiary lymphoid structures observed in cases of Merkel cell carcinoma showing spontaneous regression. (PubMed, Exp Dermatol)
Gene set enrichment analysis between MCPyV-positive and TLS-positive samples and other samples showed significantly high enrichment of "B-cell-mediated immunity" gene sets in the MCPyV-positive and TLS-positive groups. In conclusion, TLS may play an important role in the spontaneous regression of MCC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1)
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PD-L1 expression • CD20 positive
2d
ATTAC-MCC: Gene-Modified Immune Cells (FH-MCVA2TCR) in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer (clinicaltrials.gov)
P1/2, N=7, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=16 --> 7 | Trial completion date: Apr 2025 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases • Immune cell
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HLA-A (Major Histocompatibility Complex, Class I, A)
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HLA-A*02
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Keytruda (pembrolizumab) • Bavencio (avelumab) • Actimmune (interferon gamma-1 b) • MCC1 TCR
8d
Knockdown of nicotinamide N-methyltransferase suppresses proliferation, migration, and chemoresistance of Merkel cell carcinoma cells in vitro. (PubMed, Hum Cell)
Data obtained clearly demonstrated that NNMT knockdown is associated with a decrease of cell proliferation, viability, and migration, as well as with enhanced sensitivity to treatment with chemotherapeutic drugs. Taken together, these results suggest that NNMT could represent an interesting MCC biomarker and a promising target for targeted anti-cancer therapy.
Preclinical • Journal
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NNMT (Nicotinamide N-Methyltransferase)
10d
ADAM: Adjuvant Avelumab in Merkel Cell Cancer (clinicaltrials.gov)
P3, N=101, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Feb 2029 | Trial primary completion date: Jul 2025 --> Apr 2026
Enrollment closed • Trial completion date • Trial primary completion date • IO biomarker
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Bavencio (avelumab)
13d
Neoadjuvant Nivolumab and Relatlimab in Merkel Cell Carcinoma (clinicaltrials.gov)
P2, N=20, Recruiting, Melanoma Institute Australia | Not yet recruiting --> Recruiting
Enrollment open
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TMB (Tumor Mutational Burden)
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PD-L1 expression
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PD-L1 IHC 28-8 pharmDx
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Opdualag (nivolumab/relatlimab) • relatlimab (BMS-986016)
21d
AURELIO-03: Study of SO-C101 and SO-C101 in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
P1, N=200, Active, not recruiting, SOTIO Biotech AG | Trial completion date: Dec 2023 --> Nov 2024 | Trial primary completion date: Dec 2023 --> Aug 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Keytruda (pembrolizumab) • nanrilkefusp alfa (SOT101)
24d
Safety and effectiveness of avelumab in patients with Merkel cell carcinoma in general clinical practice in Japan: Post-marketing surveillance. (PubMed, J Dermatol)
This PMS confirmed the clinical tolerability and effectiveness of avelumab in patients with MCC, with no new safety concerns. The risk-benefit profile of avelumab was comparable with that observed in clinical trials and remains favorable for use in general clinical practice in Japan.
P4 data • Journal
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PD-L1 (Programmed death ligand 1)
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Bavencio (avelumab)
29d
Trial completion
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Keytruda (pembrolizumab)
1m
ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer. (PubMed, Cancers (Basel))
Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC.
Journal
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CEACAM5 (CEA Cell Adhesion Molecule 5) • NKX2-1 (NK2 Homeobox 1) • CEACAM6 (CEA Cell Adhesion Molecule 6) • KRT20 (Keratin 20) • ATOH1 (Atonal BHLH Transcription Factor 1) • TFAP2A (Transcription Factor AP-2 Alpha)
1m
TRPS1 expression in non-melanocytic cutaneous neoplasms: an immunohistochemical analysis of 200 cases. (PubMed, J Pathol Transl Med)
Our study shows that TRPS1 may be an effective discriminatory marker for BCCs and SCCs. It also has a role in distinguishing BCCs from EMPSGCs.
Journal
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TRPS1 (Transcriptional Repressor GATA Binding 1)
1m
High-Risk Skin Cancers With Atezolizumab Plus NT-I7 (clinicaltrials.gov)
P1/2, N=31, Terminated, NeoImmuneTech | Phase classification: P1b/2a --> P1/2 | N=84 --> 31 | Trial completion date: May 2024 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2024 --> Aug 2023; Strategic decision by sponsor
Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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BRAF (B-raf proto-oncogene)
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Tecentriq (atezolizumab) • Hyleukin-7 (efineptakin alfa)
1m
Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers (clinicaltrials.gov)
P1, N=23, Active, not recruiting, TuHURA Biosciences, Inc. | Trial completion date: Dec 2023 --> Mar 2024 | Recruiting --> Active, not recruiting
Enrollment closed • Trial completion date • Metastases
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IFx-2.0
1m
ABILITY: A Beta-only IL-2 ImmunoTherapY Study (clinicaltrials.gov)
P1/2, N=115, Recruiting, Medicenna Therapeutics, Inc. | Trial primary completion date: Sep 2024 --> Jun 2026
Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
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Keytruda (pembrolizumab) • MDNA11
1m
Evaluation of an Investigational Software for Analysis of Microsatellite Instability in Multiple Cutaneous Cancers (USCAP 2024)
PCR analysis using the Promega OncoMate® MSI Dx Analysis System with an investigational data interpretation software correlates with evaluation of MMR expression by IHC in 94% of cases, among the tumor types evaluated. MSI-high results reliably (100% in this sample) predict loss of MMR protein IHC staining, but occasional cases yield MSS results while having MMR loss by IHC.
Microsatellite instability • MSi-H Biomarker • IO biomarker
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MSI (Microsatellite instability)
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MSI-H/dMMR
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OncoMate™ MSI
1m
Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study. (PubMed, J Dermatol)
The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.
Journal
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TNFRSF8 (TNF Receptor Superfamily Member 8)
1m
A Trial To Find Out If Vidutolimod Together With Cemiplimab Is Safe And If It Works In Adult Participants With Advanced Cancer Or Metastatic Cancer (clinicaltrials.gov)
P2, N=225, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Mar 2027 --> Jul 2027 | Trial primary completion date: Mar 2027 --> Jul 2027
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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Libtayo (cemiplimab-rwlc) • vidutolimod (CMP-001)
1m
Alliance A091605: Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma (clinicaltrials.gov)
P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Sep 2024
Trial completion date • Metastases
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CD4 (CD4 Molecule)
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Keytruda (pembrolizumab)
1m
Phase classification • Combination therapy • Metastases
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MSI (Microsatellite instability)
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MSI-H/dMMR
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • Imfinzi (durvalumab) • Bavencio (avelumab) • plinabulin (BPI 2358)
1m
Cytomorphological traits of fine-needle aspirates of hyalinizing trabecular tumor of the thyroid gland: A brief report. (PubMed, Indian J Pathol Microbiol)
However, its cytomorphological traits are helpful in the diagnosis. In combination with FNAC, immunohistochemistry, and molecular testing, HTT can be accurately diagnosed.
Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600
1m
PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer. (PubMed, Int J Mol Sci)
Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.
Review • Journal • IO biomarker
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PRAME (Preferentially Expressed Antigen In Melanoma)
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PRAME expression
1m
Avelumab in the Treatment of Advanced Merkel Cell Carcinoma: A Systematic Review. (PubMed, Dermatol Surg)
Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.
Review • Journal • Metastases
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PD-L1 (Programmed death ligand 1)
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Bavencio (avelumab)
2ms
Merkel cell polyomavirus-specific and CD39+CLA+ CD8 T cells as blood-based predictive biomarkers for PD-1 blockade in Merkel cell carcinoma. (PubMed, Cell Rep Med)
Conversely, frequencies of CD39+CD103+ CD8 T cells are associated with tumor burden and worse outcomes. These cell subsets can be useful as biomarkers and to isolate blood-derived tumor-specific T cells.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • ITGAE (Integrin Subunit Alpha E) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
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TMB-L • ENTPD1 expression
2ms
Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma. (PubMed, Cell Rep Med)
These results suggest that cancer-specific CD8 T cells in the blood may play a role in anti-PD-1 responses. Thus, strategies that augment their number or mobilize them into tumors could improve outcomes.
Journal
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CD8 (cluster of differentiation 8)
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Opdivo (nivolumab)
2ms
Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient. (PubMed, Nat Commun)
We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD4 (CD4 Molecule)
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Keytruda (pembrolizumab)
2ms
Journal
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SSTR (Somatostatin Receptor)
2ms
Merkel Cell Carcinoma and the Eye. (PubMed, Clin Dermatol)
Eyelid MCC treatments include Mohs micrographic surgery to allow for complete clearance and adequate reconstruction of lost tissue, followed by adjuvant radiotherapy. In advanced disease, immunotherapies are preferred over traditional chemotherapy and are a subject of ongoing research.
Journal • IO biomarker
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NKX2-1 (NK2 Homeobox 1)
2ms
Studies of Dermatologic Diseases Biospecimen Acquisition Protocol (clinicaltrials.gov)
P=N/A, N=700, Recruiting, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | N=500 --> 700
Enrollment change
2ms
PNeoVCA: Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors (clinicaltrials.gov)
P1, N=36, Recruiting, Mayo Clinic | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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TMB-H
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Keytruda (pembrolizumab) • cyclophosphamide • Leukine (sargramostim) • neoantigen peptide vaccine
2ms
Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling. (PubMed, Sci Adv)
Last, pharmacologic inhibition of mTOR or mtROS reversed MCC-PD-1:PD-L1-dependent proliferation and synergized with PD-1 checkpoint blockade in suppressing tumorigenesis. Our results identify an MCC-PD-1-mTOR-mtROS axis as a tumor growth-accelerating mechanism, the blockade of which might contribute to clinical response in patients with MCC.
Journal • PD(L)-1 Biomarker • IO biomarker • Tumor cell
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PD-L2 (Programmed Cell Death 1 Ligand 2)
2ms
LT and SOX9 expression are associated with gene sets that distinguish Merkel cell polyomavirus-positive and -negative Merkel cell carcinoma. (PubMed, Br J Dermatol)
Tumours with weak expression of LT tend to co-express genes related to squamous differentiation and cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • CDK6 (Cyclin-dependent kinase 6) • SOX9 (SRY-Box Transcription Factor 9) • SNAI1 (Snail Family Transcriptional Repressor 1)
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TMB-H • SNAI1 expression • SOX9 expression
2ms
Tumor-Associated Macrophages in Merkel Cell Carcinoma: Old Balances, New Checks. (PubMed, Clin Cancer Res)
These data improve our understanding about why some tumors with brisk tumor-infiltrating lymphocytes do not respond to immunotherapy and provide a compelling rationale to target myeloid checkpoints in MCC. See related article by Tabachnick-Cherny et al., p. xxxx.
Journal
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S100A8 (S100 Calcium Binding Protein A8)
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S100A8 expression
3ms
BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors (clinicaltrials.gov)
P1/2, N=110, Recruiting, Sotio Biotech Inc. | Trial completion date: Jul 2039 --> Dec 2041 | Trial primary completion date: Jul 2024 --> Apr 2026
Trial completion date • Trial primary completion date • Metastases
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset) • GPC3 (Glypican 3)
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EGFR mutation • ALK translocation • GPC3 expression • BRCA mutation • GPC3 overexpression
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cyclophosphamide • BOXR1030
3ms
Testing the Combination of Two Anticancer Drugs M1774 (Tuvusertib) and Avelumab to Evaluate Their Safety and Effectiveness in Treating Merkel Cell Skin Cancer, MATRiX Trial (clinicaltrials.gov)
P2, N=50, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Jun 2025 --> Jan 2028 | Initiation date: Dec 2023 --> Sep 2024 | Trial primary completion date: Jun 2025 --> Jan 2028
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Metastases
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Bavencio (avelumab) • tuvusertib (M1774)
3ms
The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases. (PubMed, Infect Agent Cancer)
This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression
3ms
Enhancing immunogenic responses through CDK4/6 and HIF2α inhibition in Merkel cell carcinoma. (PubMed, Heliyon)
This study reveals that the CDK4/6 inhibitor, palbociclib can enhance PD-L1 gene transcription and surface expression in MCC cells by activating HIF2α...Simultaneously, co-targeting CDK4/6 and HIF2α boosts ROS levels while suppressing SLC7A11, a key regulator of cellular redox balance, promoting ferroptosis- a form of immunogenic cell death linked to iron. Considering the rising importance of immunogenic cell death in immunotherapy, this strategy holds promise for improving future MCC treatments, markedly increasing immunogenic cell death various across various MCC cell lines, thus advancing cancer immunotherapy.
Journal • PD(L)-1 Biomarker • IO biomarker
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EPAS1 (Endothelial PAS domain protein 1) • SLC7A11 (Solute Carrier Family 7 Member 11)
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Ibrance (palbociclib)
3ms
Genetic Risk Factors for Early-Onset Merkel Cell Carcinoma. (PubMed, JAMA Dermatol)
Additional variants in DNA repair genes were also identified among patients with MCC. Because variants in certain DNA repair and cancer predisposition genes are associated with early-onset MCC, genetic counseling and testing should be considered for patients presenting at younger than 50 years.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
3ms
Tumor-associated Macrophages in Merkel Cell Carcinoma: Old Balances, New Checks. (PubMed, Clin Cancer Res)
A recent report sheds light on the tumor-associated macrophages (TAMs) in MCC, and the association of S100A8-expressing TAMs with resistance to anti-PD-(L)1 inhibitors. These data improve our understanding about why some tumors with brisk TIL do not respond to immunotherapy and provide a compelling rationale to target myeloid checkpoints in MCC.
Journal
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S100A8 (S100 Calcium Binding Protein A8)
|
S100A8 expression
3ms
Trial completion date • Trial primary completion date • IO biomarker
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TMB (Tumor Mutational Burden)
|
PD-L1 expression
|
Bavencio (avelumab)
3ms
Trial completion date • Trial primary completion date • Combination therapy • Oncolytic virus • IO biomarker
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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PD-L1 expression • BRAF V600E • EGFR mutation • BRAF V600 • ALK rearrangement
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Opdivo (nivolumab) • MEM-288
3ms
TORCH: LITT and Pembrolizumab in Recurrent Brain Metastasis (clinicaltrials.gov)
P1, N=10, Terminated, University of Florida | N=16 --> 10 | Active, not recruiting --> Terminated; Sponsor terminated
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
|
Keytruda (pembrolizumab)
3ms
Phase classification • Metastases
|
vusolimogene oderparepvec (RP1)