Additionally, phospho-STAT3 levels negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.

over 1 year ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)

CDK6 overexpression • RB1 positive

2years

First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML (clinicaltrials.gov)

P1a/1b, N=9, Terminated, Shengke Pharmaceuticals Pty Ltd | N=67 --> 9 | Recruiting --> Terminated; The reasons for early termination is due to slow recruitment

2 years ago

Enrollment change • Trial termination

FLT3 (Fms-related tyrosine kinase 3) • RB1 (RB Transcriptional Corepressor 1)

RB1 positive

ETH-155008

over2years

Anaplastic Large Cell Transformation of Mycosis Fungoides: Case Report and Review of the Literature. (PubMed, Am J Dermatopathol)

Because clinical behavior and therapeutic options of tMF and primary cutaneous ALCL may be different, it is clinically relevant to differentiate these 2 entities. The proof of clonal relationship may be useful in diagnostically challenging cases with features overlapping between tMF and primary cutaneous ALCL.

over 2 years ago

Review • Journal • IO biomarker

ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • IRF4 (Interferon regulatory factor 4) • SOCS1 (Suppressor Of Cytokine Signaling 1) • DUSP22 (Dual Specificity Phosphatase 22) • USP22 (Ubiquitin Specific Peptidase 22) • TRG (T Cell Receptor Gamma Locus)

TP53 mutation • ALK rearrangement • RB1 positive

over2years

Development of novel palbociclib-based CDK4/6 inhibitors exploring the back pocket behind the gatekeeper. (PubMed, Invest New Drugs)

The intracellular inhibition of CDK4/6 by 17m was confirmed by western blot analysis of the levels of phosphorylated Rb in MDA-MB-453 cells. With respect to the metabolic stability, compound 17m possessed longer half-life (t) in mouse liver microsome than palbociclib.

over 2 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • CDK2 (Cyclin-dependent kinase 2) • CDK7 (Cyclin Dependent Kinase 7) • CDK9 (Cyclin Dependent Kinase 9) • CDK1 (Cyclin-dependent kinase 1) • CDK3 (Cyclin Dependent Kinase 3)

HER-2 negative • RB1 positive

Ibrance (palbociclib)

over2years

Association of Merkel Cell Polyomavirus Status With p53, RB1, and PD-L1 Expression and Patient Prognosis in Merkel Cell Carcinomas: Clinical, Morphologic, and Immunohistochemical Evaluation of 17 Cases. (PubMed, Appl Immunohistochem Mol Morphol)

Our data demonstrated that RB1 was effective for immunohistochemically investigating the MCPyV status of tumors. TPS was superior to the combined positive score in evaluating PD-L1 in MCC. Tumor-infiltrating lymphocytes were the only parameters that were associated with survival. Further studies with larger series are required to confirm these results.

over 2 years ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

PD-L1 expression • TP53 expression • RB1 positive

over2years

Branchioma with a nested/organoid morphology: molecular profiling of a distinctive potentially misleading variant and reappraisal of potential relationship to CD34-positive/Rb1-deficient tumors of the neck. (PubMed, Virchows Arch)

FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.

over 2 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • MSH6 (MutS homolog 6) • CD34 (CD34 molecule) • SYP (Synaptophysin)

KRAS mutation • PTEN mutation • HRAS mutation • CD34 positive • RB1 positive

TruSight Oncology 500 Assay

over2years

High Red Blood Cell Distribution Width to Platelet Ratio is an Independent Poor Prognostic Factor in Patients with Newly Diagnosed Multiple Myeloma. (PubMed, Discov Med)

RPR is a practical and effective prognostic marker in newly diagnosed patients with MM, and a high RPR is an independent poor prognostic factor.

over 2 years ago

Journal

RB1 (RB Transcriptional Corepressor 1) • NCAM1 (Neural cell adhesion molecule 1)

RB1 positive

almost3years

First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML (clinicaltrials.gov)

P1a/1b, N=67, Recruiting, Shengke Pharmaceuticals Pty Ltd | Active, not recruiting --> Recruiting

almost 3 years ago

Enrollment open

FLT3 (Fms-related tyrosine kinase 3) • RB1 (RB Transcriptional Corepressor 1)

RB1 positive

ETH-155008

almost3years

First-in Human (FIH) Trial of ETH-155008 in Subjects With B-NHL, CLL/SLL and AML (clinicaltrials.gov)

P1a/1b, N=9, Active, not recruiting, Shengke Pharmaceuticals Pty Ltd | Recruiting --> Active, not recruiting | N=67 --> 9

almost 3 years ago

Enrollment closed • Enrollment change

FLT3 (Fms-related tyrosine kinase 3) • RB1 (RB Transcriptional Corepressor 1)

RB1 positive

ETH-155008

3years

Retinoblastoma protein as an intrinsic BRD4 inhibitor modulates small molecule BET inhibitor sensitivity in cancer. (PubMed, Nat Commun)

BET inhibitor resistance in RB-deficient cells is abolished by co-administration of CREB inhibitor. Our study identifies RB protein as a bona fide intrinsic inhibitor of BRD4 and demonstrates that RB inactivation confers resistance to small molecule BET inhibitors, thereby revealing a regulatory hub that converges RB upstream signaling onto BRD4 functions in diseases such as cancer.

3 years ago

Journal

CDK4 (Cyclin-dependent kinase 4) • BRD4 (Bromodomain Containing 4)

RB1 positive

3years

PALATINUS: Safety And Efficacy Study Of Palbociclib Plus Cetuximab Versus Cetuximab To Treat Head And Neck Cancer (clinicaltrials.gov)

P2, N=124, Completed, Pfizer | Active, not recruiting --> Completed

3 years ago

Trial completion • Metastases

RB1 (RB Transcriptional Corepressor 1)

CDKN2A negative • RB1 positive

Erbitux (cetuximab) • Ibrance (palbociclib)

3years

CDK4/6 initiates Rb inactivation and CDK2 activity coordinates cell-cycle commitment and G1/S transition. (PubMed, Sci Rep)

Together, our data suggest that CDK4/6 inactivates Rb to begin E2F and CDK2 activation, and high CDK2 activity is necessary and sufficient to generate a bistable switch for Rb phosphorylation before DNA replication. These findings highlight how cells initiate the cell cycle and subsequently commit to the cell cycle before the G1/S transition.

3 years ago

Journal

CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2)

CCNE1 overexpression • RB1 positive