TAM kinase inhibition and immune checkpoint blockade– a winning combination in cancer treatment?

Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.

(2020) Thomas Yau et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase I/II trial of sitravatinib (sitra) combined with nivolumab (nivo) in patients (pts) with advanced clear cell renal cell cancer (aCCRCC) that progressed on prior VEGF-targeted therapy.

(2020) Pavlos Msaouel et al.   JOURNAL OF CLINICAL ONCOLOGY

Cabozantinib in combination with atezolizumab in non-small cell lung cancer (NSCLC) patients previously treated with an immune checkpoint inhibitor: Results from cohort 7 of the COSMIC-021 study.

(2020) Joel W. Neal et al.   JOURNAL OF CLINICAL ONCOLOGY

Cabozantinib in combination with atezolizumab in urothelial carcinoma previously treated with platinum-containing chemotherapy: Results from cohort 2 of the COSMIC-021 study.

(2020) Sumanta K. Pal et al.   JOURNAL OF CLINICAL ONCOLOGY

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study.

(2020) Neeraj Agarwal et al.   JOURNAL OF CLINICAL ONCOLOGY

Immune checkpoint inhibitor toxicities: systems-based approaches to improve patient care and research

(2020) Douglas B Johnson et al.   LANCET ONCOLOGY

Pan-TAM tyrosine kinase inhibitor BMS-777607 enhances anti-PD-1 mAb efficacy in a murine model of triple-negative breast cancer

(2019) Canan Kasikara et al.   CANCER RESEARCH

Immuno-Oncological Efficacy of RXDX-106, a Novel Small Molecule Inhibitor of the TAM (TYRO3, AXL, MER) Family of Kinases

(2019) Yumi Yokoyama et al.   CANCER RESEARCH

Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

(2019) David J. Pinato et al.   BRITISH JOURNAL OF CANCER

A Niche-Dependent Myeloid Transcriptome Signature Defines Dormant Myeloma Cells

(2019) Weng Hua Khoo et al.   BLOOD

Targeting Protein Kinases to Enhance the Response to anti-PD-1/PD-L1 Immunotherapy

(2019) Marilina García-Aranda et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Myeloma sleeper agent in myeloid disguise

(2019) Binod Dhakal et al.   BLOOD

MERTK Acts as a Costimulatory Receptor on Human CD8+ T Cells

(2019) Marlies J.W. Peeters et al.   Cancer Immunology Research

Cabozantinib in Combination with Immunotherapy for Advanced Renal Cell Carcinoma and Urothelial Carcinoma: Rationale and Clinical Evidence

(2019) Paulo Bergerot et al.   MOLECULAR CANCER THERAPEUTICS

Mechanisms of Resistance to PD-1 and PD-L1 Blockade

(2018) Theodore S. Nowicki et al.   CANCER JOURNAL

Results of phase I plus expansion cohorts of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus ipilimumab (Ipi) in patients (pts) with with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies.

(2018) Rosa Maria Nadal et al.   JOURNAL OF CLINICAL ONCOLOGY

Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing

(2018) Hira Rizvi et al.   JOURNAL OF CLINICAL ONCOLOGY

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

(2018) Luís Eduardo Zucca et al.   UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS

Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors

(2018) Aaron M. Goodman et al.   JAMA Oncology

Immune oncology, immune responsiveness and the theory of everything

(2018) Tolga Turan et al.   Journal for ImmunoTherapy of Cancer

Does Axl have potential as a therapeutic target in pancreatic cancer?

(2018) Wenting Du et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

1129OStage 2 enrollment complete: Sitravatinib in combination with nivolumab in NSCLC patients progressing on prior checkpoint inhibitor therapy

(2018) T A Leal et al.   ANNALS OF ONCOLOGY

872PPhase Ib study (COSMIC-021) of cabozantinib in combination with atezolizumab: Results of the dose escalation stage in patients (pts) with treatment-naïve advanced renal cell carcinoma (RCC)

(2018) N Agarwal et al.   ANNALS OF ONCOLOGY

Long-Term Survival in Patients Responding to Anti–PD-1/PD-L1 Therapy and Disease Outcome upon Treatment Discontinuation

(2018) Marie-Léa Gauci et al.   CLINICAL CANCER RESEARCH

Management of immune-related adverse events resulting from immune checkpoint blockade

(2018) Barouyr Baroudjian et al.   Expert Review of Anticancer Therapy

AXL Is a Putative Tumor Suppressor and Dormancy Regulator in Prostate Cancer

(2018) Haley D. Axelrod et al.   MOLECULAR CANCER RESEARCH

The Emerging Role of TYRO3 as a Therapeutic Target in Cancer

(2018) Sherri Smart et al.   Cancers

The TAM receptor Tyro3 regulates myelination in the central nervous system

(2017) Rainer Akkermann et al.   GLIA

A microRNA-7/growth arrest specific 6/TYRO3 axis regulates the growth and invasiveness of sorafenib-resistant cells in human hepatocellular carcinoma

(2017) Tasnuva D. Kabir et al.   HEPATOLOGY

TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy

(2017) Yemsratch T. Akalu et al.   IMMUNOLOGICAL REVIEWS

Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

(2017) Andrea B. Apolo et al.   JOURNAL OF CLINICAL ONCOLOGY

Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase

(2017) Koji Nomura et al.   JOURNAL OF IMMUNOLOGY

Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

(2017) Arjun V Balar et al.   LANCET

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial

(2017) Achim Rittmeyer et al.   LANCET

Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial

(2017) Anthony B El-Khoueiry et al.   LANCET

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study

(2017) Arjun V Balar et al.   LANCET ONCOLOGY

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial

(2017) Padmanee Sharma et al.   LANCET ONCOLOGY

Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression

(2017) Canan Kasikara et al.   MOLECULAR CANCER RESEARCH

Pharmacoproteomic characterisation of human colon and rectal cancer

(2017) Martin Frejno et al.   Molecular Systems Biology

Effective combinatorial immunotherapy for castration-resistant prostate cancer

(2017) Xin Lu et al.   NATURE

Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer

(2017) Scott J. Antonia et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

(2017) Joaquim Bellmunt et al.   NEW ENGLAND JOURNAL OF MEDICINE

Key Roles of AXL and MER Receptor Tyrosine Kinases in Resistance to Multiple Anticancer Therapies

(2017) Marie Schoumacher et al.   Current Oncology Reports

Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models

(2017) Zhiqiang Guo et al.   Oncotarget

Phospho-AXL is widely expressed in glioblastoma and associated with significant shorter overall survival

(2017) Julia Onken et al.   Oncotarget

Protein S drives oral squamous cell carcinoma tumorigenicity through regulation of AXL

(2017) Ghada Abboud-Jarrous et al.   Oncotarget

Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma

(2016) Willy Hugo et al.   CELL

Distinct Receptor Tyrosine Kinase Subsets Mediate Anti-HER2 Drug Resistance in Breast Cancer

(2016) Peter B. Alexander et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Safety and Efficacy of Durvalumab (MEDI4736), an Anti–Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer

(2016) Christophe Massard et al.   JOURNAL OF CLINICAL ONCOLOGY

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial

(2016) Roy S Herbst et al.   LANCET

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial

(2016) Jonathan E Rosenberg et al.   LANCET

Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study

(2016) Corey J Langer et al.   LANCET ONCOLOGY

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

(2016) Martin Reck et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting TYRO3 inhibits epithelial–mesenchymal transition and increases drug sensitivity in colon cancer

(2016) C-W Chien et al.   ONCOGENE

Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

(2016) Shohei Koyama et al.   Nature Communications

Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer

(2016) Valsamo Anagnostou et al.   Cancer Discovery

TAM receptors Tyro3 and Mer as novel targets in colorectal cancer

(2016) Robin Schmitz et al.   Oncotarget

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

(2016) Magdalena Paolino et al.   Cancers

Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma

(2016) Jian Liu et al.   PLoS One

TAM Receptor Signaling in Immune Homeostasis

(2015) Carla V. Rothlin et al.   Annual Review of Immunology

AXL Mediates Resistance to PI3Kα Inhibition by Activating the EGFR/PKC/mTOR Axis in Head and Neck and Esophageal Squamous Cell Carcinomas

(2015) Moshe Elkabets et al.   CANCER CELL

Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression

(2015) YAN DUAN et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

MERTK as negative regulator of human T cell activation

(2015) Raquel Cabezo´n et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial

(2015) Antoni Ribas et al.   LANCET ONCOLOGY

Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial

(2015) Jeffrey S Weber et al.   LANCET ONCOLOGY

Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination

(2015) Yuki Miyamoto et al.   MOLECULAR BIOLOGY OF THE CELL

Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity

(2015) Stefani Spranger et al.   NATURE

Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma

(2015) Michael A. Postow et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer

(2015) Edward B. Garon et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

(2015) Julie Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

(2015) Hossein Borghaei et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

(2015) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab versus Ipilimumab in Advanced Melanoma

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma

(2015) L Zhou et al.   ONCOGENE

Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma

(2015) Kuo-Chou Chiu et al.   ORAL ONCOLOGY

Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer

(2015) N. A. Rizvi et al.   SCIENCE

The future of immune checkpoint therapy

(2015) P. Sharma et al.   SCIENCE

Antagonists of PD-1 and PD-L1 in Cancer Treatment

(2015) Evan J. Lipson et al.   SEMINARS IN ONCOLOGY

Optimization of multi-stage dynamic treatment regimes utilizing accumulated data

(2015) Xuelin Huang et al.   STATISTICS IN MEDICINE

Mer receptor tyrosine kinase is frequently overexpressed in human non-small cell lung cancer, confirming resistance to erlotinib

(2015) Shengzhi Xie et al.   Oncotarget

MerTK is a novel therapeutic target in gastric cancer

(2015) Jun Ho Yi et al.   Oncotarget

Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma

(2015) Parag P. Patwardhan et al.   Oncotarget

Kinome-wide shRNA Screen Identifies the Receptor Tyrosine Kinase AXL as a Key Regulator for Mesenchymal Glioblastoma Stem-like Cells

(2015) Peng Cheng et al.   Stem Cell Reports

AXL kinase as a novel target for cancer therapy

(2015) Xiaoliang Wu et al.   Oncotarget

GAS6/AXL Axis Regulates Prostate Cancer Invasion, Proliferation, and Survival in the Bone Marrow Niche

(2015) Yusuke Shiozawa et al.   NEOPLASIA

AXL Mediates Resistance to Cetuximab Therapy

(2014) T. M. Brand et al.   CANCER RESEARCH

CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T-cell Checkpoint Immunotherapy in Pancreatic Cancer Models

(2014) Y. Zhu et al.   CANCER RESEARCH

Receptor Tyrosine Kinases, TYRO3, AXL, and MER, Demonstrate Distinct Patterns and Complex Regulation of Ligand-induced Activation

(2014) Wen-I Tsou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells

(2014) Magdalena Paolino et al.   NATURE

Diversification of TAM receptor tyrosine kinase function

(2014) Anna Zagórska et al.   NATURE IMMUNOLOGY

Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities

(2014) Erin D Lew et al.   eLife

Evaluation of Tyro3 Expression, Gas6-Mediated Akt Phosphorylation, and the Impact of Anti-Tyro3 Antibodies in Melanoma Cell Lines

(2013) Stephen J. Demarest et al.   BIOCHEMISTRY

Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab

(2013) Christiane Meyer et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

T Cell-Derived Protein S Engages TAM Receptor Signaling in Dendritic Cells to Control the Magnitude of the Immune Response

(2013) Eugenio A. Carrera Silva et al.   IMMUNITY

MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis

(2013) Rebecca S. Cook et al.   JOURNAL OF CLINICAL INVESTIGATION

MERTK receptor tyrosine kinase is a therapeutic target in melanoma

(2013) Jennifer Schlegel et al.   JOURNAL OF CLINICAL INVESTIGATION

Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

(2013) Tyler R. Simpson et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia

(2013) A B Lee-Sherick et al.   ONCOGENE

Axl/Gas6/NFκB signalling in schwannoma pathological proliferation, adhesion and survival

(2013) S Ammoun et al.   ONCOGENE

MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL

(2013) Kathryn A. Tworkoski et al.   Pigment Cell & Melanoma Research

Systemic Autoimmunity in TAM Triple Knockout Mice Causes Inflammatory Brain Damage and Cell Death

(2013) Qiutang Li et al.   PLoS One

Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer

(2013) L. Bosurgi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway

(2013) Jingchao Xu et al.   TUMOR BIOLOGY

Axl is essential for VEGF-A-dependent activation of PI3K/Akt

(2012) Guo-Xiang Ruan et al.   EMBO JOURNAL

Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation

(2012) Jennifer Landsberg et al.   NATURE

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

(2012) Julie R. Brahmer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme

(2012) Y Wang et al.   ONCOGENE

Activation of TYRO3/AXL Tyrosine Kinase Receptors in Thyroid Cancer

(2011) E. Avilla et al.   CANCER RESEARCH

Targeting Axl and Mer Kinases in Cancer

(2011) A. Verma et al.   MOLECULAR CANCER THERAPEUTICS

Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, Simultaneously Suppresses Metastasis, Angiogenesis, and Tumor Growth

(2011) F. M. Yakes et al.   MOLECULAR CANCER THERAPEUTICS

R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer

(2010) S. J. Holland et al.   CANCER RESEARCH

Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis

(2010) Nora B Caberoy et al.   EMBO JOURNAL

TNF-α, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages

(2010) Federica Alciato et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

(2009) S. Loges et al.   BLOOD

Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal

(2009) Brian T Fife et al.   NATURE IMMUNOLOGY

Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival

(2009) C. Gjerdrum et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Axl and Growth Arrest Specific Gene 6 Are Frequently Overexpressed in Human Gliomas and Predict Poor Prognosis in Patients with Glioblastoma Multiforme

(2008) M. Hutterer et al.   CLINICAL CANCER RESEARCH