Albert Einstein Cancer Center

Selected Achievements: Experimental Therapeutics

The Horwitz laboratory demonstrated that discodermolide has a distinct pose in the Taxol binding pocket that drives a complementary mode of microtubule stabilization. This led to the synthesis of active, hybrid molecules that incorporate properties of both drugs (Biochemistry. 48:11664-77, 2009. PMID 19863156; J Med Chem. 54:6319-27, 2011. PMID 21870795) 


The Perez-Soler laboratory reported that menadione causes EGFR activation and prevents EGFR dephosphorylation by erlotinib and cetuximab, observations that led to an ongoing clinical trial with a topical preparation to assess its impact on EGFR inhibitor- associated dermatitis (Clin Cancer Res 17, 6766-6777, 2011. PMID 21914790) 


The Almo and Nathenson laboratories defined the spatial and organizational constraints that control the localization and signaling of PD-1/PD-L1 and PD-1/L2 complexes within the immunological synapse providing a basis for manipulating the PD-1 pathways for immunotherapy. (Proc Natl Acad Sci U S A 105:10483-10488, 2008. PMID 18641123) 


The Goldman laboratory reported that a novel proton-coupled folate transporter, active in the acidic microenvironment of solid tumors, has a high affinity for the new generation antifolate, pemetrexed (Mol Pharmacol. 74:854-62, 2008. PMID 18524888) 


The Kalpana laboratory reported that suppression of Aurora Kinase A, shown to be a downstream target of IN1/SNG5, markedly inhibits the growth and increases apoptosis of rhabdoid cancer cell lines, providing a rationale for the use of inhibitors of Aurora Kinase A in the treatment of this disease.  (Cancer Res. 71:3225, 2011. PMID 21521802) 


Sparano reported that the farnesyl transferase inhibitor (FTI) tipifarnib significantly inhibited FTase enzyme activity and p-STAT3 expression in primary tumors, resulting in a high pathologic complete response rate when combined with neoadjuvant doxorubicin/cyclophosphamide which met the primary efficacy endpoint (Clin Cancer Res. 15:2942-8, 2009. PMID 19351752)  


Sparano and his collaborators established that weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (N Engl J Med 358:1663-1671, 2008. PMID 18420499) 


Einstein and his collaborators in gynecological oncology reported that adjuvant radiation therapy sandwiched between chemotherapy improved survival for uterine papillary serous carcinoma (UPSC) and carcinosarcoma, especially when the primary tumors were completely resected. This approach is being tested as an arm in clinical trials for the treatment of aggressive uterine cancers – Einstein, Huang, Hou, Goldberg. (Gynecol Oncol. 124:21-5, 2011. PMID 22035806; Gynecol Oncol. 124:26-30, 2011, PMID 22055846)  


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