Oncogenic ALK signaling.

Slides:

Advertisements

Similar presentations

BRF Begin with BRAF Searching for a target in metastatic melanoma?

Advertisements

 2013 Genentech USA, Inc. All rights reserved. Disclosure/Disclaimer The Molecular Basis of Lung Cancer slide presentation is not an independent educational.

In vivo animal model studies in biological science 1.Cancer 2. Neuroscience 1.Cancer research 2. Neuroscience.

Gene Transcription G0G0 G1G1 Priming S G2G2 M Cell Cell Cycle Growth Factors + Growth Factors & Cell Cycle Receptors.

The Cell Cycle and Cancer AP Biology. Cell Cycle Numerous genes control the cell cycle They regulate the progression through checkpoints. A sensor detects.

Tyrosine Kinases as Targets for Cancer Therapy Krause DS, Van Etten RA N Engl J Med 2005;353(2): Krause DS, Van Etten RA N Engl J Med 2005;353(2):

ETV1 IS A LINEAGE SURVIVAL FACTOR THAT COOPERATES WITH KIT IN GASTROINTESTINAL STROMAL TUMORS Introduction Tim Butler March 8 th, 2012.

Clinicopathologic Features of EML4-ALK Mutant Lung Cancer Shaw AT et al. ASCO 2009; Abstract (Poster)

Samsung Genome Institute Samsung Medical Center

Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non- small cell lung cancer: Focus on epidermal growth factor receptor.

Lung Cancer Tumour Markers

Figure 1. Resistance mechanism against first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). (A) Mutations in the EGFR.

Daniela Sia, Augusto Villanueva, Scott L. Friedman, Josep M. Llovet

Inhibition of FGFR fusion kinase activity repressed tumor growth in a mouse xenograft model. Inhibition of FGFR fusion kinase activity repressed tumor.

The Kinase-Independent, Second Life of CDK6 in Transcription

Summary of genetic alterations in resistant biopsies among patients progressing on ceritinib or alectinib. Summary of genetic alterations in resistant.

Positioning NK-κB in multiple myeloma

Chapter 17: Regulation of cell number

Nat. Rev. Clin. Oncol. doi: /nrclinonc

Figure 3 The cell cycle and the role of CDK4/6 inhibition

Cell to Cell Communication via Enzyme Linked Receptors

Nat. Rev. Clin. Oncol. doi: /nrclinonc

Extracellular Regulation of Apoptosis

Figure 1 A schematic representation of the HER2 signalling pathway

BIOLOGY 12 Cancer.

Daniela Sia, Augusto Villanueva, Scott L. Friedman, Josep M. Llovet

Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer Roberto Ferrara, MD, Nathalie Auger, MD, Edouard Auclin,

Schematic representation of main EGFR-TKIs resistance mechanisms.

Targeted Therapies in Melanoma: Translational Research at Its Finest

Intrinsic and acquired trastuzumab resistance.

PTEN Tumor Suppressor and Cancer

Schematic view of Trk receptors signalling, showing the three major pathways involved in cell differentiation and survival. Schematic view of Trk receptors.

The chimeric Trk protein, composed by the TK domain with ATPase activity and a TM loop along with a fusion partner. The chimeric Trk protein, composed.

Valerie D. Myers et al. BTS 2018;3:

The role of WNT signaling in sprouting angiogenesis.

Peter Celec, Yoshikazu Yonemitsu Pathophysiology

Vascular Endothelial Growth Factor (VEGF) Pathway

Volume 139, Issue 2, Pages e3 (August 2010)

NOTCH and PI3K-AKT Pathways Intertwined

William G. Nelson, Michael C. Haffner, Srinivasan Yegnasubramanian

Proposed spiral model for prostate cancer progression.

Platelet-derived growth factor (PDGF) signalling pathway.

Canonical gliomagenesis mediators EGFR, P53, and retinoblastoma protein (RB1) are important for cancer signaling. Canonical gliomagenesis mediators EGFR,

Molecular Characterization of Acquired Resistance to the BRAF Inhibitor Dabrafenib in a Patient with BRAF-Mutant Non–Small-Cell Lung Cancer Charles M.

The p53 pathway is involved in the inhibition of cell proliferation observed in 15-LOX-1-overexpressing cells. The p53 pathway is involved in the inhibition.

Friends with Benefits: Microenvironmental NRG1β and HGF Mediate HER2-Targeted Resistance in L-HER2+ and HER2E Breast Cancer Sarah B. Crist, Cyrus M.

Model for the regulation of HIPK2 activity and p53 phosphorylations by the ATM pathway. Model for the regulation of HIPK2 activity and p53 phosphorylations.

ALK resistance mutations predict for sensitivity to lorlatinib in patient-derived cell line models of acquired resistance to ceritinib. ALK resistance.

PKM2 is tyrosine phosphorylated and inhibited by FGFR1 in cancer cells with oncogenic or overexpressed FGFR1. PKM2 is tyrosine phosphorylated and inhibited.

Protein expression profile in a dasatinib-resistant cell line.

Nat. Rev. Clin. Oncol. doi: /nrclinonc

MiR-200c is a PI3K–AKT signaling pathway regulator in CRC

Location of common clinically relevant mutations in EGFR

Simplified BRAF signaling network.

Figure 2 Mechanisms of RET activation in cancer

TYK2 signaling in T-ALL. TYK2 signaling in T-ALL. TYK2 activates STAT1 through phosphorylation downstream of the IL-10 receptor. Once phosphorylated, STAT.

p53 loss affects several steps of the metastatic process.

Structural organization of ALK and its fusion proteins.

The critical roles of miR-23a and miR-27a in colorectal cancer progression. miR-23a primarily increases cell motility through downregulation of its target.

Western blotting confirming the presence of fusion proteins in tumor lysates and showing increased signaling pathway activation in respective tumors. Western.

No single ALK mutations confer high-level resistance to lorlatinib.

Model of immunosuppressive drug action in lymphocyte activation.

Although equivalent experimental systems have been employed in a variety of assessments to determine BCR-ABL1 kinase domain mutation sensitivity on the.

Schematic representation of signaling pathways associated with cannabinoid receptor activation induced by its agonists. Schematic representation of signaling.

Connections between insulin/insulin-like growth factor 1 signaling and metabolic pathways in tumor cells. Connections between insulin/insulin-like growth.

Overview of molecular JAK signaling.

Regulation of signaling by wild-type and oncogenic Ras.

Driver pathways and key genes in OSCC

Presentation transcript:

Oncogenic ALK signaling. Oncogenic ALK signaling. The ALK fusion protein is constitutively active and signals via phospholipase Cγ (PLCγ), JAK–STAT, RAS–RAF–MEK–ERK, and PI3K–AKT–mTOR pathways (13). This signaling results in the aberrant regulation of a number of genes (some of which are represented here), ultimately driving cell-cycle progression, survival, proliferation, and angiogenesis (50). Secondary mutations in the ALK kinase domain (starred) cause acquired resistance to ALK TKIs. Several of the bypass signaling tracks implicated in ALK TKI resistance are also shown here—EGFR, HER2/HER3, MET, KIT, and IGF1R with their respective ligands. Jessica J. Lin et al. Cancer Discov 2017;7:137-155 ©2017 by American Association for Cancer Research