To the best of our knowledge, this is the first clinical case report in the literature describing the benefit of anlotinib and sintilimab treatment for non-small cell lung cancer with RET fusion and high PD-L1 expression. This study explores the biomarker selection for targeted therapy and combined immunotherapy in NSCLC patients.

12 months ago

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

PD-L1 (Programmed death ligand 1) • RET (Ret Proto-Oncogene)

PD-L1 expression • PD-L1 overexpression • RET fusion • RET expression

Focus V (anlotinib) • Tyvyt (sintilimab)

1year

GDNF family receptor alpha-like (GFRAL) expression is restricted to the caudal brainstem. (PubMed, Mol Metab)

Through highly sensitive and selective technologies we show Gfral expression is overwhelmingly restricted to the brainstem and expect that GDF15 and GFRAL-based therapies in development for cancer cachexia will specifically target AP/NTS cells.

1 year ago

Journal

RET (Ret Proto-Oncogene) • GDF15 (Growth differentiation factor 15)

RET expression

1year

When multiple primary lung cancers express the same rare mutation: a case report. (PubMed, Front Oncol)

Thus, the patient was considered to have multiple primary lung cancers. In such cases, whole-exome sequencing can distinguish whether the nodules have the exact origin.

1 year ago

Journal

RET (Ret Proto-Oncogene)

RET mutation • RET expression

1year

YAP regulates HER3 signaling-driven adaptive resistance to RET inhibitors in RET-aberrant cancer. (PubMed, Clin Cancer Res)

The YAP-HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment.

1 year ago

Journal

RET (Ret Proto-Oncogene) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

RET fusion • ERBB3 expression • RET expression • RET positive

Gilotrif (afatinib) • Retevmo (selpercatinib) • Gavreto (pralsetinib) • Visudyne (verteporfin)

over1year

Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma. (PubMed, Curr Issues Mol Biol)

As observed in other tumors, we presume striking interactions between NF-κB, Nrf2, and Phox2B, which might constitute an important crosstalk triangle, whose decompensation may trigger a more aggressive phenotype. Consequently, these transcription factors could be a promising target for novel therapeutic approaches and hence, further investigation on their regulation in neuroblastoma shall be reinforced.

over 1 year ago

Review • Journal

NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • PHOX2B (Paired Like Homeobox 2B)

RET expression

almost2years

Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. (PubMed, Cancer Sci)

Dual inhibition of RET and CDK8 restricted cell proliferation by producing multimodal oxidative stress responses in treated cells. Our data suggest that epigenetically enhanced RET protects KMT2A-r AML cells from oxidative stresses, which could be exploited as a potential therapeutic strategy.

almost 2 years ago

Journal

RET (Ret Proto-Oncogene) • KMT2A (Lysine Methyltransferase 2A) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

MLL rearrangement • KMT2A expression • RET expression

almost2years

Therapeutic strategy using novel RET/YES1 dual-target inhibitor in lung cancer. (PubMed, Biomed Pharmacother)

In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.

almost 2 years ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • CCDC6 (Coiled-Coil Domain Containing 6) • CTTN (Cortactin)

EGFR mutation • ALK mutation • RET mutation • MET mutation • RET rearrangement • RET expression • RET positive

Tagrisso (osimertinib) • dasatinib • PLD-101

2years

RET enhancer haplotype-dependent remodeling of the human fetal gut development program. (PubMed, PLoS Genet)

We show that their knockdown in human neuroblastoma SK-N-SH cells reduces RET and/or EDNRB gene expression, expanding the RET-EDNRB GRN. The human embryos we studied had major remodeling of the gut transcriptome but were unlikely to have had HSCR: thus, genetic or epigenetic changes in addition to those in RET are required for aganglionosis.

2 years ago

Journal

EDNRB (Endothelin Receptor Type B)

RET expression

2years

Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target. (PubMed, Hum Cell)

Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored.

2 years ago

Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • FLT1 (Fms-related tyrosine kinase 1) • FLT4 (Fms-related tyrosine kinase 4) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • FCGR2A (Fc fragment of IgG receptor IIa) • PDGFA (Platelet Derived Growth Factor Subunit A) • PDGFB (Platelet Derived Growth Factor Subunit B) • FCGR2B (Fc Fragment Of IgG Receptor IIb)

MET overexpression • MET expression • AXL overexpression • FGFR1 expression • FLT1 expression • RET expression

2years

Efficacy, safety and translational study of pyrotinib combined with albumin-bound paclitaxel as firstline treatment of HER-2 positive metastatic breast cancer (SABCS 2023)

This study demonstrates that pyrotinib in combination with albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and a manageable safety for patients with HER-2-positive metastatic breast cancer after adjuvant and/or neoadjuvant trastuzumab therapy. PFS was shorter in patients with visceral metastases. TLR3 and RET were the proteins that significantly associated with PFS in patients.

2 years ago

Clinical • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ABL1 (ABL proto-oncogene 1) • CEACAM5 (CEA Cell Adhesion Molecule 5) • TLR3 (Toll Like Receptor 3) • WIF1 (WNT Inhibitory Factor 1) • CCN1 (Cellular Communication Network Factor 1)

HER-2 positive • HR positive • RET expression

Herceptin (trastuzumab) • Irene (pyrotinib) • albumin-bound paclitaxel

2years

HEPATOCYTE-SPECIFIC GROWTH DIFFERENTIATION FACTOR 15 OVEREXPRESSION AMELIORATES HIGH-FAT DIET-INDUCED OBESITY AND LIVER STEATOSIS VIA INDUCTION OF FIBROBLAST GROWTH FACTOR 21 IN MICE (AASLD 2023)

From a different point of view, it has been reported to improve glucose intolerance due to its potent anti-obesity effect, and NAFLD by enhancing metformin action in diabetic mouse models... GDF15 and FGF21, both liver-derived cellular stress response mitokines, have their blood levels increased in NAFLD. Recently, direct effects of GDF15 on the liver were reported, and in this study, induction of FGF21 expression in the liver was demonstrated under GDF15 overexpression.

2 years ago

Preclinical • IO biomarker

CCR4 (C-C Motif Chemokine Receptor 4) • GDF15 (Growth differentiation factor 15) • TGFB1 (Transforming Growth Factor Beta 1) • FGF21 (Fibroblast Growth Factor 21)

GDF15 overexpression • RET expression

metformin

2years

Targeting the RET tyrosine kinase in neuroblastoma: a review and application of a novel selective drug design strategy. (PubMed, Biochem Pharmacol)

Here, we review the background of RET as a potential therapeutic target in neuroblastoma tumors and the results of recent preclinical studies and clinical trials evaluating the safety and efficacy of RET inhibition in adults and children. We also present a novel approach to drug discovery leveraging the chemical phenomenon of atropisomerism to develop specific RET inhibitors and present preliminary data demonstrating the efficacy of a novel RET inhibitor against neuroblastoma tumor cells.

2 years ago

Review • Journal

RET (Ret Proto-Oncogene)

RET mutation • RET rearrangement • RET expression