Wirkstoffe G

Galeterone

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.

Link to Drug Information Portal, a service of the U.S. National Library of Medicine, National Institutes of Health

Link to National Cancer Institute
Link zu Wiki

Antiandrogens

Ganetespib

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

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

Ganitumab

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.

Link to Drug Information Portal, a service of the U.S. National Library of Medicine, National Institutes of Health
Link to National Cancer Institute
Link zu Wiki

Monoclonal Antibodies against tumors

Gefitinib - IRESSA®

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.
 
Link zur Fachinformation des Arzneimittel-Kompendiums der Schweiz:
Medikamenteniformation: Für den Arzt  Patienteninformation
Information des Médicaments:  Info prof. Info patient
Informazione sul medicamento: info per il paziente
 

More Information in English:

Link to National Cancer Institute
Link zu Wiki
Link zu PharmaWiki
Link to European Medicines Agency (EMEA)Link to Physicians Desk Reference (PDR)

 
More Information for patients:
Gemcitabin

Gemzar ® - The hydrochloride salt of an analogue of the antimetabolite nucleoside deoxycytidine with antineoplastic activity.

Indikationen/Anwendungsmöglichkeiten gemäss Arzneimittel-Kompendium der Schweiz®:
Gemcitabin ist 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 Arzneimittel-Kompendium der Schweiz

Info for Patients presented by Scott Hamilton from Chemocare.com

Zytostatikum

Gemtuzumab Ozogamicin

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.

According to WIKI In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA

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 to European Medicines Agency (EMEA)
Info for Patients presented by Scott Hamilton from Chemocare.com

Monoclonal antibodies for tumors

Glasdegib