According to the NCI website Galeterone is an orally bioavailable small-molecule androgen receptor modulator and CYP17 lyase inhibitor with potential antiandrogen activity. Galeterone exhibits three distinct mechanisms of action: 1) as an androgen receptor antagonist, 2) as a CYP17 lyase inhibitor and 3) by decreasing overall androgen receptor levels in prostate cancer tumors, all of which may result in a decrease in androgen-dependent growth signaling.
According to the NCI website Ganetespib is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Ganetespib binds to and inhibits Hsp90, resulting in the proteasomal degradation of oncogenic client proteins, the inhibition of cell proliferation and the elevation of heat shock protein 72 (Hsp72); it may inhibit the activity of multiple kinases, such as c-Kit, EGFR, and Bcr-Abl, which as client proteins depend on functional HsP90 for maintenance. Hsp90, a 90 kDa molecular chaperone upregulated in a variety of tumor cells, plays a key role in the conformational maturation, stability and function of "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
Abstract from Molecular Cancer Therapeutics:
Targeted inhibition of the molecular chaperone heat shock protein 90 (Hsp90) results in the simultaneous blockade of multiple oncogenic signaling pathways and has thus emerged as an attractive strategy for the development of novel cancer therapeutics. Ganetespib (formerly known as STA-9090) is a unique resorcinolic triazolone inhibitor of Hsp90 currently in clinical trials for a number of human cancers. Here we show that ganetespib exhibits potent in vitro cytotoxicity in a range of solid and hematological tumor cell lines, including those that express mutated kinases that confer resistance to small molecule tyrosine kinase inhibitors (TKIs). Ganetespib treatment rapidly induced the degradation of known Hsp90 client proteins, displayed superior potency to the ansamycin inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), and exhibited sustained activity even with short exposure times. In vivo, ganetespib demonstrated potent antitumor efficacy in solid and hematological xenograft models of oncogene addiction, as evidenced by significant growth inhibition and/or regressions. Of note, evaluation of the microregional activity of ganetespib in tumor xenografts showed that ganetespib efficiently distributed throughout tumor tissue, including hypoxic regions >150 μm from the microvasculature, to inhibit proliferation and induce apoptosis. Importantly, ganetespib showed no evidence of cardiac or liver toxicity. Taken together, this preclinical activity profile suggests that ganetespib may have broad application for a variety of human malignancies, and with select mechanistic and safety advantages over other first- and second-generation Hsp90 inhibitors. Molecular Cancer Therapeutics
According to the NCI website ganitumab is a recombinant, fully human monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Ganitumab binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R is a tyrosine kinase and a member of the insulin receptor family. IGF-1R activation stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been highly implicated in tumorigenesis and metastasis.
Alternative Names according to Adis Insight: GDA-201; NAM NK cells - Gamida; NAM-NK Cells; Nicotinamide Expanded Haploidentical or Mismatched Related Donor Natural Killer Cells
Published: Mar 02, 2020
Gefitinib - IRESSA® ist ein Anilinochinazolin mit antineoplastischer Aktivität. Gefitinib hemmt die katalytische Aktivität zahlreicher Tyrosinkinasen einschließlich des epidermalen Wachstumsfaktorrezeptors (EGFR), was zur Hemmung des Tyrosinkinase-abhängigen Tumorwachstums führen kann. Insbesondere konkurriert Gefitinib mit der Bindung von ATP an die Tyrosin-Kinase-Domäne von EGFR um damit die Rezeptor-Autophosphorylierung zu hemmen und letztlich die Hemmung der Signalübertragung. Gefitinib kann auch den Stillstand des Zellzyklus induzieren und die Angiogenese hemmen.
Indikationen/Anwendungsmöglichkeiten gemäss Arzneimittel-Kompendium der Schweiz®:
- IRESSA ist indiziert zur Behandlung von Patienten mit Adenokarzinom der Lunge und aktivierender EGFR Mutation, wenn eine platinhaltige Chemotherapie versagt hat oder nicht möglich ist.
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The hydrochloride salt of an analogue of the antimetabolite nucleoside deoxycytidine with antineoplastic activity.
Indikationen/Anwendungsmöglichkeiten gemäss Compendium®:
Gemzar® ist laut Compendium® indiziert
- zur palliativen Behandlung von Patienten mit fortgeschrittenem oder metastasierendem nicht- kleinzelligem Lungenkarzinom.
- zur Behandlung von Patienten mit lokal fortgeschrittenem (Stadium II oder III) oder metastasierendem Pankreas-Adenokarzinom. Dies gilt auch für mit 5-FU vorbehandelte Patienten.
- zur Behandlung bei inoperablem, lokal fortgeschrittenem oder metastasierendem Blasenkarzinom in Kombination mit Cisplatin.
- in Kombination mit Carboplatin zur Behandlung von Patientinnen mit rezidivierendem Ovarialkarzinom nach einer mindestens 6 Monate zurückliegenden platinhaltigen Therapie.
- in Kombination mit Paclitaxel zur Behandlung von Patientinnen mit nicht operablem, lokal wiederauftretendem oder metastasierendem Mammakarzinom, bei denen es nach einer adjuvanten/neoadjuvanten Chemotherapie zu einem Rezidiv kam. Die vorausgegangene Chemotherapie sollte ein Anthracyclin enthalten haben, sofern dieses nicht klinisch kontraindiziert war.
Link to Drug Information Portal, a service of the U.S. National Library of Medicine, National Institutes of Health
Link to MedlinePlus, a service of the U.S. National Library of Medicine, National Institutes of Health
Link to National Cancer Institute
Link zu Wiki
Link zu PharmaWiki
Link to Physicians Desk Reference (PDR)
Link to European Medicines Agency (EMEA)
Link zur Fachinformation des Compendium®
Info for Patients presented by Scott Hamilton from Chemocare.com
According to the NCI website, the anti-CD3/CD20 bispecific antibody GEN3013 is a bispecific monoclonal antibody, with potential immunomodulating and antineoplastic activities. Anti-CD20/CD3 monoclonal antibody GEN3013 contains two antigen-recognition sites: one for human CD3, a T-cell surface antigen, and one for human CD20, a tumor-associated antigen (TAA) that is exclusively expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell malignancies. Upon administration, GEN3013 binds to both T cells and CD20-expressing B-lineage tumor cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against the CD20-expressing tumor B cells. Check for active clinical trials using this agent.
According to the NCI gemtuzumab ozogamicin is a recombinant, humanized anti-CD33 monoclonal antibody attached to the cytotoxic antitumor antibiotic calicheamicin. In this conjugate, the antibody binds to and is internalized by tumor cells expressing CD33 antigen (a sialic acid-dependent glycoprotein commonly found on the surface of leukemic blasts), thereby delivering the attached calicheamicin to CD33-expressing tumor cells. Calicheamicin binds to the minor groove of DNA, causing double strand DNA breaks and resulting in inhibition of DNA synthesis.
Indikationen/Anwendungsmöglichkeiten gemäss Chemocare.com:
Gemtuzumab ozogamicin is used to treat patients with CD33 positive acute myeloid leukemia (AML) in first relapse who are 60 years of age or older and for whom other chemotherapy is not recommenced.
Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.
- Mylotarg wird angewendet für die Kombinationstherapie mit Daunorubicin (DNR) und Cytarabin (AraC) zur Behandlung von erwachsenen Patienten mit nicht vorbehandelter, neu diagnostizierter CD33‑positiver akuter myeloischer Leukämie (AML), ausgenommen akuter Promyelozytenleukämie (APL) (siehe «Warnhinweise und Vorsichtsmassnahmen» und «Klinische Wirksamkeit»).
According to the NCI website Gilteritinib is an orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) FMS-related tyrosine kinase 3 (FLT3, STK1, or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246), with potential antineoplastic activity. Gilteritinib binds to and inhibits both the wild-type and mutated forms of FLT3, AXL and ALK. This may result in an inhibition of FLT3, AXL, and ALK-mediated signal transduction pathways and reduction of tumor cell proliferation in cancer cell types that overexpress these RTKs. FLT3, AXL and ALK, overexpressed or mutated in a variety of cancer cell types, play a key role in tumor cell growth and survival. Check for active clinical trials using this agent.
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According to the NCI website glasdegib maleate is the salt form of glasdegib, an orally bioavailable small-molecule, smoothened (SMO) receptor inhibitor, with potential antineoplastic activity. Upon oral administration, glasdegib targets, binds to and inhibits the activity of SMO. This inhibits the activity of the Hedgehog (Hh) signaling pathway and inhibits the growth of tumor cells in which this pathway is aberrantly activated. SMO, a transmembrane protein, is involved in Hh signal transduction. The Hh signaling pathway plays an important role in cellular growth, differentiation, repair, and cancer stem cell (CSC) survival. Constitutive activation of Hh pathway signaling has been observed in various types of malignancies and is associated with uncontrolled cellular proliferation in a variety of cancers. Check for active clinical trials using this agent.
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According to the NCI website, 9-ING-41 is a maleimide-based, small molecule inhibitor of glycogen synthase kinase-3 (GSK-3; serine/threonine-protein kinase GSK3) with potential antineoplastic activity. Upon intravenous administration, 9-ING-41 binds to and competitively inhibits GSK-3, which may lead to downregulation of nuclear factor kappa B (NF-kappaB) and decreased expression of NF-kappaB target genes including cyclin D1, B-cell lymphoma 2 (Bcl-2), anti-apoptotic protein XIAP, and B-cell lymphoma extra-large (Bcl-XL). This may inhibit NF-kappaB-mediated survival and chemoresistance in certain tumor types. GSK-3, a constitutively active serine/threonine kinase that plays a role in numerous pathways involved in protein synthesis, cellular proliferation, differentiation, and metabolism, is aberrantly overexpressed in certain tumor types and may promote tumor cell survival and resistance to chemotherapy and radiotherapy. Check for active clinical trials using this agent. (NCI Thesaurus)
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