Charlotte Kopitz

Anetumab Ravtansine - a Novel Mesothelin-Targeting Antibody-Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect

Mesothelin is a tumor differentiation antigen frequently overexpressed in tumors such as mesothelioma, ovarian, pancreatic, and lung adenocarcinomas while showing limited expression in nonmalignant tissues. Mesothelin is therefore an attractive target for cancer therapy using antibody–drug conjugates (ADC). This study describes the detailed characterization of anetumab ravtansine, here referred to as BAY 94-9343, a novel ADC consisting of a human anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4 via a disulfide-containing linker. Binding properties of the anti-mesothelin antibody were analyzed using surface plasmon resonance, immunohistochemistry, flow cytometry, and fluorescence microscopy. Effects of BAY 94-9343 on cell proliferation were first studied in vitro and subsequently in vivo using subcutaneous, orthotopic, and patient-derived xenograft tumor models. The antibody binds to human mesothelin with high affinity and selectivity, thereby inducing efficient antigen internalization. In vitro, BAY 94-9343 demonstrated potent and selective cytotoxicity of mesothelin-expressing cells with an IC50 of 0.72 nmol/L, without affecting mesothelin-negative or nonproliferating cells. In vivo, BAY 94-9343 localized specifically to mesothelin-positive tumors and inhibited tumor growth in both subcutaneous and orthotopic xenograft models. In addition, BAY 94-9343 was able to induce a bystander effect on neighboring mesothelin-negative tumor cells. Antitumor efficacy of BAY 94-9343 correlated with the amount of mesothelin expressed and was generally superior to that of standard-of-care regimen resulting in complete tumor eradication in most of the models. BAY 94-9343 is a selective and highly potent ADC, and our data support its development for the treatment of patients with mesothelin-expressing tumors. Mol Cancer Ther; 13(6); 1537–48. ©2014 AACR.

Preclinical efficacy of the auristatin-based antibody-drug conjugate BAY 1187982 for the treatment of FGFR2-positive solid tumors.

The fibroblast growth factor receptor FGFR2 is overexpressed in a variety of solid tumors, including breast, gastric, and ovarian tumors, where it offers a potential therapeutic target. In this study, we present evidence of the preclinical efficacy of BAY 1187982, a novel antibody-drug conjugate (ADC). It consists of a fully human FGFR2 monoclonal antibody (mAb BAY 1179470), which binds to the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated through a noncleavable linker to a novel derivative of the microtubule-disrupting cytotoxic drug auristatin (FGFR2-ADC). In FGFR2-expressing cancer cell lines, this FGFR2-ADC exhibited potency in the low nanomolar to subnanomolar range and was more than 100-fold selective against FGFR2-negative cell lines. High expression levels of FGFR2 in cells correlated with efficient internalization, efficacy, and cytotoxic effects in vitro Pharmacokinetic analyses in mice bearing FGFR2-positive NCI-H716 tumors indicated that the toxophore metabolite of FGFR2-ADC was enriched more than 30-fold in tumors compared with healthy tissues. Efficacy studies demonstrated that FGFR2-ADC treatment leads to a significant tumor growth inhibition or tumor regression of cell line-based or patient-derived xenograft models of human gastric or breast cancer. Furthermore, FGFR2 amplification or mRNA overexpression predicted high efficacy in both of these types of in vivo model systems. Taken together, our results strongly support the clinical evaluation of BAY 1187982 in cancer patients and a phase I study (NCT02368951) has been initiated. Cancer Res; 76(21); 6331-9. ©2016 AACR.

Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

Molecular mechanisms underlying the development of resistance to platinum‐based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance‐related factors. In this study, we used human whole‐genome microarrays and linear model analysis to identify potential resistance‐related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum‐resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance‐related genes in the A2780cis tumor model. Although A2780‐bearing mice showed a strong carboplatin‐induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis‐bearing mice showed no further increase after short‐term or long‐term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin‐treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal‐enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control‐transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin‐treated shGDF15‐A2780cis tumors. Furthermore, shRNA‐mediated GDF15 knockdown abrogated p27 expression as compared to control‐transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum‐resistant ovarian cancer.

Abstract 772: Anti-tumor efficacy of the selective pan-FGFR Inhibitor BAY 1163877 in preclinical squamous cell carcinoma models of different origin

Squamous cell carcinoma (SCC) is a common subtype of lung cancer and is strongly associated with smoking. In contrast to adenocarcinomas of the lung, SCCs do not significantly harbor epidermal growth factor (EGFR) mutations or ALK, ROS1 or RET translocations, which are therapeutically tractable. SCC of the lung and SCC of the head and neck region and esophagus not only share risk factors, morphologic features and mechanisms of tumorigenesis but also frequent fibroblast growth factor receptor 1 (FGFR1) gene alterations. In addition, we found that FGFR2 and FGFR3 expression were also altered in patient derived models of SCC of various origins. FGFRs may thus represent viable therapeutic targets for the treatment of SCC. BAY 1163877, an orally available and potent inhibitor of FGFR1, FGFR2 and FGFR3, inhibited SCC cell proliferation as well as downstream FGFR signaling in vitro. When applied in vivo, BAY 1163877 was able to reduce growth of a FGFR1-overexpressing lung SCC xenograft model, a FGFR1-overexpressing esophageal SCC xenograft model, and a FGFR3-overexpressing head and neck SCC xenograft model, achieving reductions in tumor growth by 67 to 92% as compared to the vehicle control. BAY 1163877 was very well tolerated in all models performed. These data suggest that selective inhibition of FGFR1 to 3 with BAY 1163877 might have therapeutic potential for the treatment of SCC malignancies. A phase I clinical trial (NCT01976741) to determine the safety, tolerability and recommended Phase 2 dose in advanced cancer patients is ongoing. Citation Format: Melanie Heroult, Matthias Ocker, Charlotte Kopitz, Dieter Zopf, Andrea Hagebarth, Karl Ziegelbauer, Stuart Ince, Peter Ellinghaus. Anti-tumor efficacy of the selective pan-FGFR Inhibitor BAY 1163877 in preclinical squamous cell carcinoma models of different origin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 772. doi:10.1158/1538-7445.AM2015-772

Abstract 4491: FGFR2-ADC potently and selectively inhibits growth of gastric and breast cancer xenograft models

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for treatment of cancer. We have developed a novel ADC directed against fibroblast growth factor receptor 2 (FGFR2). FGFR2 is overexpressed in several cancer indications, such as gastric cancer and breast cancer, thus representing an interesting therapeutic target for the treatment of FGFR2 positive cancer patients with an ADC-based therapy. The FGFR2-ADC consists of the fully human anti-FGFR2-mAb BAY 1179470 conjugated via a stable linker to a novel auristatin cytotoxic agent (technology licensed from Seattle Genetics). The FGFR2-mAb BAY 1179470, which is cross-reactive with human, mouse, rat and monkey, induces internalization of FGFR2. Quantitative data on FGFR2 antibody bound per cell (ABC) were determined with the QuantiBrite assay using BAY 1179470. FGFR2-ADC has a potency in the single digit nM to sub nM range in a panel of FGFR2-positive cells lines (e.g., SNU-16, KatoIII, SUM52-PE, MFM-223) and shows more than 100-fold selectivity versus FGFR2-negative cell lines. High levels of FGFR2 on cancer cells correlate with internalization efficacy and cytotoxic activity in vitro. FGFR2-ADC is highly efficacious in monotherapy and results in tumor growth inhibition in the gastric cancer xenograft model SNU-16 and tumor regression in the breast cancer xenograft model MFM-223. At doses efficacious in mice, FGFR2-ADC is well tolerated. The pre-clinical efficacy and tolerability data obtained for FGFR2-ADC suggest a therapeutic index and support clinical testing. Citation Format: Anette Sommer, Carl F. Nising, Christoph Mahlert, Charlotte C. Kopitz, Hans-Georg Lerchen, Simone Greven, Beatrix Stelte-Ludwig, Joachim Schuhmacher, Ruprecht Zierz, Sabine Wittemer-Rump, Christoph Schatz, Frank Reetz, Heiner Apeler, Rolf Jautelat, Bertolt Kreft, Karl Ziegelbauer. FGFR2-ADC potently and selectively inhibits growth of gastric and breast cancer xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4491. doi:10.1158/1538-7445.AM2014-4491

Abstract 1683: Pharmacokinetic/pharmacodynamic (PK/PD) and toxicokinetic/toxicodynamic (TK/TD) modeling of preclinical data of FGFR2-ADC (BAY 1187982) to guide dosing in phase 1

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA BAY 1187982 is an antibody drug conjugate (ADC) directed against fibroblast growth factor receptor 2 (FGFR2). FGFR2 is overexpressed in several cancer indications, such as gastric, breast, and ovarian cancer. Anti-tumor efficacy of BAY 1187982 has been demonstrated in several FGFR2-positive cancer cell line as well as patient-derived xenograft models. Toxicology findings from repeated dose preclinical safety studies in monkeys indicated effects related to the liver, kidney, heart and coagulation system. To predict the therapeutic index of BAY 1187982 in humans and to support the design of the first-in-human (FIH) study with respect to selection of dose and regimen, preclinical efficacy and toxicity findings were quantified. All available preclinical PK, TK, tumor response and toxicity data from mouse models and monkey studies were used to create a model framework to describe the PK, TK, PK/PD and TK/TD relationship as functions of BAY 1187982 dose, regimen and time. Human PK parameters based on scaling from monkey were used to predict PK profiles in humans for a range of doses and schedules. These sets of predicted exposure models were combined with the PK/PD as well as the TK/TD model to assess the expected efficacy (according to RECIST criteria) and toxicity range in humans, respectively. The dosing schedule leading to the largest therapeutic index and the dose escalation schema for the FIH study were determined. The FIH study is currently under preparation. Citation Format: Sabine Wittemer-Rump, Anette Sommer, Charlotte Kopitz, Hung Huynh, Christoph Schatz, Ruprecht Zierz, Manuela Braun, Kirstin Meyer, Dirk Laurent, Jorg Lippert, Klaas Prins. Pharmacokinetic/pharmacodynamic (PK/PD) and toxicokinetic/toxicodynamic (TK/TD) modeling of preclinical data of FGFR2-ADC (BAY 1187982) to guide dosing in phase 1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1683. doi:10.1158/1538-7445.AM2015-1683

Abstract 1684: Preclinical anti-tumor efficacy of FGFR2-ADC BAY 1187982 in patient-derived gastric, breast and ovarian cancer models

Antibody-drug conjugates (ADC) represent a promising therapeutic approach for treatment of cancer. We have developed a novel ADC directed against fibroblast growth factor receptor 2 (FGFR2). FGFR2 is overexpressed in several cancer indications, such as gastric, breast, and ovarian cancer and thus represents a potential therapeutic target for treatment of FGFR2-positive cancer patients with ADC-based therapy. FGFR2-ADC consists of a fully human anti-FGFR2-Ab (BAY 1179470) conjugated via a stable linker to a novel auristatin cytotoxic agent licensed from Seattle Genetics. FGFR2-ADC exhibits low nM to sub-nM potency in vitro in a panel of FGFR2-positive cancer cells lines (SNU-16, MFM-223, NCI-H716) while being inactive against FGFR2-low or -negative cell lines (MDA-MB-231, HEK-293, BaF/3) and highly selective versus a control ADC. FGFR2-ADC is highly efficacious in monotherapy and results in tumor growth inhibition in the gastric cancer xenograft model SNU-16 and tumor regression in the breast cancer xenograft model MFM-223. FGFR2-ADC induces tumor stasis in the colorectal cancer xenograft model NCI-H716 and regrown tumors are sensitive to a second treatment cycle of FGFR2-ADC. FGFR2-ADC shows high efficacy in vivo in monotherapy in patient-derived (PDX) FGFR2-positive murine xenograft models, e.g. in the ovarian cancer model OV30-0511A. FGFR2-ADC is also efficacious in the gastric cancer PDX model GC10-0608 and the breast cancer model MAXF857. The toxophore metabolite of FGFR2-ADC was more than 30-fold enriched in tumors versus other organs (liver, spleen, kidneys) in NCI-H716 tumor-bearing mice. Based on the preclinical efficacy, PK and tolerability data, evaluation of FGFR2-ADC in cancer patients appears warranted. A Phase I study is planned. Citation Format: Anette Sommer, Charlotte Kopitz, Christoph Schatz, Ruprecht Zierz, Joachim Schuhmacher, Sabine Wittemer-Rump, Klaas Prins, Manuela Braun, Frank Reetz, Bertolt Kreft, Hung T. Huynh, Karl Ziegelbauer. Preclinical anti-tumor efficacy of FGFR2-ADC BAY 1187982 in patient-derived gastric, breast and ovarian cancer models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1684. doi:10.1158/1538-7445.AM2015-1684

Abstract 4766: Pharmacodynamic and stratification biomarker for the anti-FGFR2 antibody (BAY1179470) and the FGFR2-ADC

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA We are developing a novel fibroblast growth factor receptor 2 (FGFR2) directed antibody (BAY 1179470) as well as an FGFR2-antibody drug conjugate (FGFR2-ADC) for cancer therapy. FGFR2 is expressed in a range of tumor types such as gastric, breast, HNSCC, pancreatic and ovarian cancers. FGFR2 has been described to promote tumor growth and survival and play a role in chemotherapy resistance. In this study, we aim to identify stratification and pharmacodynamic biomarkers for two antibody-based anti-FGFR2 therapies in preclinical models. As potential biomarkers, FGFR2 antigen expression levels were investigated in tumors by FGFR2 immunohistochemistry (IHC), FGFR2 gene amplification by FISH, FGFR2 mRNA by RNAscope, and FGFR2 protein by mass spectrometry. Furthermore, FGFR2 levels in xenograft tumors were compared to those in clinical samples of human tumors. Efficacy of BAY 1179470 in gastric cancer tumor models with high FGFR2 expression levels was generally higher compared to models with low FGFR2 expression. SNU-16 and GC10-0608, which are characterized by high expression levels of FGFR2, had T/C values of 0.13 and 0.55 when treated with 5 mg/kg BAY 1179470. Tumor growth was not inhibited by BAY 1179470 in MKN-45 and T47D, which had no detectable FGFR2 expression. MFM-223 and NCI-H716 with high FGFR2 expression levels did not respond to BAY1179470 suggesting that they were not dependent on FGFR2 signaling. In contrast, all three established tumor models SNU-16, MFM-223, and NCI-H716 were highly responsive to FGFR2-ADC. Analysis and scoring of FGFR2 expression by IHC using human tumor samples (gastric, breast, HNSCC, pancreatic and ovarian cancer, respectively) demonstrated that tumor cell FGFR2 expression varied both within and between tumor types. IHC scoring revealed that 54% of gastric cancers, 73% of triple negative breast cancers, 90% of HNSCC, 43% of pancreatic cancers, and 43% of ovarian cancer investigated were FGFR2 positive. Within the tumor indications investigated patients showed FGFR2 expression of score 0, 1, 2 or 3 respectively.In the SNU-16 gastric cancer xenograft model, total and phospho-FGFR2 were reduced upon treatment with BAY 1179470. Depending on dose, total FGFR2 levels showed the lowest level 1-4 days after treatment and returned to baseline after 21 days. Suppression of the downstream signaling pathway component phospho-RPS6 signaling was also shown. In summary, these results demonstrate that FGFR2-directed therapies are effective in xenograft models with high FGFR2 expression. FGFR2 expression as assessed by IHC and FGFR2 gene amplifications are therefore candidate biomarkers for stratification of the FGFR2-directed studies. The anti-FGFR2 antibody BAY 1179470 is currently in Phase I testing ([NCT01881217][1]). Citation Format: Christoph A. Schatz, Charlotte Kopitz, Sabine Wittemer-Rump, Anette Sommer, Lars Lindbom, Motonobu Osada, Hiroshi Yamanouchi, Hung Huynh, Thomas Krahn, Khusru Asadullah. Pharmacodynamic and stratification biomarker for the anti-FGFR2 antibody (BAY1179470) and the FGFR2-ADC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4766. doi:10.1158/1538-7445.AM2014-4766 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01881217&atom=%2Fcanres%2F74%2F19_Supplement%2F4766.atom

Abstract 5445: Preclinical anti-tumor efficacy of an anti-C4.4a (LYPD3) antibody drug conjugate for the treatment of lung squamous cell carcinoma

C4.4a (LYPD3) has been identified previously as a cancer- and metastasis-associated internalizing cell surface protein. Targeting C4.4a with a specific antibody-drug conjugate (ADC) represents an unique opportunity to treat tumors with high unmet medical need such as squamous cell carcinomas SCC, in particular lung SCC. We have generated an anti-C4.4a ADC consisting of a fully human monoclonal antibody linked to a non cell-permeable tubulin-binding auristatin cytotoxic agent (technology licensed from Seattle Genetics). In vitro, anti-C4.4a ADC showed an anti-proliferative efficacy (IC50) in the nanomolar range in cell lines endogenously expressing C4.4a (e.g. human lung cancer cell lines NCI-H292 and NCI-H322). High ADC stability and selectivity was observed in transfected A549 lung cancer cells over-expressing C4.4a compared to mock-transfected cells. In vivo, anti-C4.4a ADC exhibited a potent and selective antitumor activity in various human xenograft models (NCI-H292, NCI-H322, SCC-4) as well as in two SCC (Lu7433, Lu7343) and one pleomorphic (Lu7064) patient-derived lung cancer xenograft models. The in vivo efficacy is strictly target-dependent and selective as no efficacy was observed in C4.4a negative models (Fadu, Lu 7700) or using a non-specific isotype antibody ADC (NCI-H292, NCI-H322). A minimal effective dose (MED) as low as 1.9 mg/kg, response rates of up to 100%, and additive anti-tumor efficacy in combination with cisplatin were observed in the NCI-H292 xenograft model. Furthermore, it has been demonstrated that NCI-H292 were still sensitive to ADC treatment when tumors were allowed to regrow after the initial treatment cycle(). The anti-C4.4a ADC, which is fully cross-reactive with the mouse orthologue of C4.4a, was well tolerated at efficacious doses. Reversible skin reddening was observed only at doses markedly higher than the MED. In summary, anti-C4.4a ADC is a promising therapeutic candidate for the treatment of C4.4a-expressing squamous cell carcinomas, andpreclinical development has been initiated. Citation Format: Joerg Willuda, Lars Linden, Hans-Georg Lerchen, Charlotte Kopitz, Sven Golfier, Ute Bach, Joachim Schumacher, Beatrix Stelte-Ludwig, Oliver Von Ahsen, Claudia Schneider, Frank Dittmer, Rudolf Beier, Sherif El-Sheik, Jan Tebbe, Gabriele Leder, Heiner Apeler, Rolf Jautelat, Bertolt Kreft, Karl Ziegelbauer. Preclinical anti-tumor efficacy of an anti-C4.4a (LYPD3) antibody drug conjugate for the treatment of lung squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5445. doi:10.1158/1538-7445.AM2014-5445

Abstract 3383: Inhibition of Akt signaling: a strategy to overcome platinum resistance in ovarian cancer.

Targeted therapies in combination with cytotoxic agents are promising future treatment regimens for women with resistant ovarian cancer. Current standard treatment of serous ovarian cancer is a platinum- (carboplatin) based chemotherapy, usually combined with taxanes. A 90% cure rate is observed in early stage ovarian cancers, however, in advanced stages, about 20-30% of patients never have a remission or will suffer from recurrent disease within 5 years. One major reason is the development of a resistance against the platinum-based chemotherapy. In order to identify possible novel therapeutic targets for platinum-resistant ovarian cancer, we compared gene expression and oncogenic kinase phosphorylation patterns in the human ovarian cancer cell line A2780 and its platinum-resistant variant A2780cis in vitro and in vivo.In vivo, the untreated A2780cis-derived tumor model showed reduced proliferation activity and enhanced apoptosis, while carboplatin treatment failed to induce tumor reduction, as compared to the sensitive A2780-derived tumor model. Analysis of 47 kinase phosphorylation sites in carboplatin-treated A2780 and A2780cis derived tumors revealed that Akt was hyperphosphorylated at Ser273 but not altered during treatment in resistant tumors, whereas Akt phosphorylation was weak and further reduced during treatment in sensitive tumors. This was associated with an unchanged p53 phosphorylation status in resistant tumors during treatment. In line with this, the novel allosteric Akt inhibitor BAY 10001931 resensitized A2780 and A2780cis cells to carboplatin in vitro. To investigate if the Akt phosphorylation status correlated with an activation of downstream targets, RNA of A2780 and A2780cis vehicle- or carboplatin treated tumors was hybridized onto an Illumina Bead Chip array. Here, linear model analysis identified GDF15 as one of four p53-induced target genes possibly involved in the development of chemoresistance. GDF15 protein expression was highly induced during carboplatin treatment in both cell lines, whereas basal GDF15 expression was higher in resistant cells than in sensitive A2780 cells in vitro and in vivo. This was correlated with a higher secretion of GDF15 into the serum of A2780cis-tumor-bearing mice. Similar tendencies were observed in vitro. Interestingly, simultaneous Akt inhibition with BAY 10001931 markedly reduced the carboplatin-induced upregulation of GDF15 in A2780 and A2780cis cells. Additionally, shRNA-mediated knockdown of GDF15 in resistant A2780cis cells also abrogated the phosphorylation of Akt in vitro. These results indicate that a causal relationship exists between Akt activation and GDF15 expression in resistant ovarian cancer cells. Together, a combination treatment with an Akt inhibitor and carboplatin of GDF15-expressing ovarian cancer cells might represent a novel approach to treat resistant ovarian cancer. Citation Format: Julia C. Meier, Bernard Haendler, Anette Sommer, Andrea Hagebarth, Georg Beckmann, Bertolt Kreft, Karl Ziegelbauer, Charlotte C. Kopitz. Inhibition of Akt signaling: a strategy to overcome platinum resistance in ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3383. doi:10.1158/1538-7445.AM2013-3383