Columbia University

Sloan-kettering Institute for Cancer Research

Owen Anthony O'Connor

Donald W Landry

Francis M Sirotnak

Jennifer Effie Amengual

Shixian Deng

Ottavio Arancio

Rosa Purgatorio

Jole Fiorito

Luigi Scotto

Shi-Xian Deng

Xiaoming Xu

Changchun Deng

Mark Lipstein

Matko Kalac

Kristen Alison Rinderspacher

Joie Fiorito

Jennifer Lue

The invention provides pharmaceutical compositions and methods for treating cancer, neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein by administering a HAT modulator and a HDAC modulator to a subject.

Histone acetyltransferase activators and compositions and uses thereof

The present disclosure provides for methods and compositions for treating cancer. A subject having lymphoma is administered an EZH2 inhibitor and an HDAC inhibitor. The combination of the EZH2 inhibitor and the HDAC inhibitor produces a synergistic effect on the cancer compared to the effect of the EZH2 inhibitor or the HDAC inhibitor alone.

Combination therapy of lymphoma

The invention provides compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.

Histone acetyltransferase activators and uses thereof

The invention relates to new compounds that reduce c-Myc expression and useful for cancer treatment, particularly hematological cancers such as aggressive B- and T-cell lymphomas. The new compounds may be combined with adjunct c-Myc inhibor agents such as a PI3K inhibitor, CK-1 inhibitor, Akt-inhibitor, proteasome inhibitor and/or mTor inhibitor. The c-Myc reducing agent may be provided as a lead-in treatment to reduce or initiate reduction of c-Myc prior to administration of the adjunct cancer therapeutic agent. Treatment with a c-Myc reducing agent modulates the disease state of the c-Myc overexpressing cancer making it less malignant and more susceptible to adjunctive cancer therapies.

Compounds for reducing c-Myc in c-Myc overexpressing cancers background

The present invention relates to the NQBS class of molecules. It is based, at least in part, on the discovery that a representative group of compounds have been observed to inhibit nuclear translocation of NF-&#x3ba;B subunits. Without being bound by any particular theory, this inhibition of nuclear translocation may be mediated by either (i) binding of the NQBS or related compound to the C-terminus of the RHD, which specifically mediates the nuclear internalization; or (ii) NQBS-mediated stabilization of the dimer/I&#x3ba;B complex, disallowing dissociation of the active NF-&#x3ba;B monomers, and thus, inhibiting the generation of the subunits necessary to enter the nucleus. The NQBS class of molecules, and related molecules, may be used in therapeutic applications where inhibition of NF-&#x3ba;B translocation is beneficial, including but not limited to the treatment of cancer, autoimmune disorders, and inflammatory states.

N-quinolin-benzensulfonamides and related compounds for the treatment of cancer, autoimmune disorders and inflammation

T cell lymphoma is treated by administering to a patient suffering from T cell lymphoma a therapeutically effective amount of 10-propargyl-10-deazaaminopterin. Remission is observed in human patients, even with drug resistant T cell lymphoma at weekly dosages levels as low as 30 mg/m. In general, the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/mper dose.

Treatment of T-cell lymphoma using 10-propargyl-10-deazaaminopterin

Sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin is assessed and patients are selected for treatment of cancer with 10-propargyl-10-deazaaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer. The polypeptide includes a member of a folate pathway polypeptide within a cell and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), &#x3b3;-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT).

Methods for assessing cancer for increased sensitivity to 10-propargyl-10-deazaaminopterin

The present invention relates to a method for assessing the sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaminopterin and a method for selecting a patient for treatment of cancer with 10-propargyl-10-deazaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer, wherein the polypeptide includes a member of folate pathways within cells and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), &#x3b3;-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT). The present invention also relates to the use of 10-propargyl-10-deazaminopterin in the treatment of multiple myeloma.

Methods to treat cancer with 10-propargyl-10-deazaaminopterin and methods for assessing cancer for increased sensitivity to 10-propargyl-10-deazaaminopterin

Lymphoma is treated using therapeutic combinations of PDX and gemcitabine by administering to a patient suffering from lymphoma a therapeutically effective amount of PDX in combination with a therapeutically effective amount of gemcitabine. The two agents can be administered together or in either order, although administration of PDX followed by gemcitabine is preferred. As in the case of MTX and Ara-C, synergism is observed, but the extent of the synergism is greater. Further, test results indicate that mechanism of action for combinations of PDX and Gem is different than for MTX and Ara-C, with more emphasis on induction of apoptosis.

Growing community of inventors

Scarsdale, NY, United States of America

Owen Anthony O'Connor