Success Stories

While chemotherapy has been vital in saving and extending the lives of cancer patients, it can also deplete the immune system of white blood cells, which are essential for fighting infections. An endogenous peptide called granulocyte colony-stimulating factor, or G-CSF, stimulates the proliferation and differentiation of a class of white blood cell called neutrophils. Scientists at Memorial Sloan-Kettering demonstrated that G-CSF accelerated the restoration of neutrophils in patients following chemotherapy, reducing the frequency and severity of infections and shortening patient recovery time. Marketed by Amgen as Neupogen® since 1991, G-CSF has been used by more than one million patients, and has become the standard of care in hospitals around the world.

Thyrogen®, or recombinant human thyroid-stimulating hormone, is used to test for recurrences of thyroid cancer in patients who have undergone a thyroidectomy. Prior to the approval of Thyrogen®, patients tested for recurrences had to be put on temporary thyroid hormone withdrawal, which can be debilitating. To date, Thyrogen®, which was licensed to Genzyme, has been taken by more than 300,000 patients and is sold in 50 countries worldwide.

While tumors can evoke an immune response, in many cases this response is ineffective. Cytokines are endogenous signaling molecules that assist in the maturation and replication of several important cell types in the immune system, and have been shown to potentiate the antitumor immune response. Scientists at Memorial Sloan-Kettering demonstrated that Interleukin-2, or IL-2, is among the most effective of the cytokines for this purpose. Marketed by Novartis Oncology as Proleukin® (aldesleukin) for injection, IL-2 was approved for the treatment of metastatic renal cell carcinoma in 1992, and for metastatic melanoma in 1998. Each year in the US, approximately three to five thousand patients are treated with Proleukin®.

Within the nucleus of our cells, the DNA is wound tightly around protein complexes called histones. Modification of histones by specialized enzymes determines just how tightly the DNA is wound. Generally, the looser the DNA-histone interaction in a particular region, the greater the expression of the genes present there. Histone deacetylase (HDAC) is an enzyme that increases the DNA-histone interaction, and thus serves to repress local gene expression.

Researchers at Memorial Sloan-Kettering and Columbia University demonstrated that HDAC inhibitors cause tumor regression, presumably through the activation of genes that suppress tumor cell growth while promoting the differentiation of normal cells. While there are now several HDAC inhibitors in development for the treatment of cancer, suberoylanilide hydroxamic acid, or Zolinza®, was the first. Zolinza®, marketed by Merck, was approved in the US for the treatment of advanced refractory cutaneous T cell lymphoma in 2006, and is in clinical trials for several other indications, including cancers of the breast, kidney, and colon.

As every molecular biologist knows, DNA cloning requires a number of steps that can be very time-consuming. Taking advantage of the ligase activity of the vaccinia virus topoisomerase I enzyme, Memorial Sloan-Kettering scientists developed a method to eliminate many of these steps, reducing the bulk of the process to a highly efficient five-minute benchtop reaction. Marketed by Invitrogen as TOPO® PCR Cloning technology, kits include standard PCR primers and a standard linearized vector with topoisomerase attached to both ends. The enzymes essentially replace themselves with the insert to be cloned, covalently attaching it to the vector. TOPO® PCR cloning does not require gel or column purification of the insert, post-PCR modification, such as digestion, blunting, or dephosphorylation, or the addition of adapters. Currently, there are 90 different products that incorporate TOPO® Cloning technology, and TOPO® Cloning products are sold in over 80 countries.

Tumors can cause bone resorption, leading to excessive levels of calcium in the blood, or hypercalcemia, which in turn can induce nausea, dehydration, stupors, and even comas. Ten to 20 percent of all cancer patients suffer from hypercalcemia. For certain cancers, such as that of the breast or lung, 30 to 40 percent of patients are hypercalcemic. Memorial Sloan-Kettering scientists demonstrated that gallium nitrate, sold by Genta under the name Ganite®, inhibits bone resorption and is an effective treatment for cancer-related hypercalcemia.

Acute promyelocytic leukemia (APL) is a rare form of leukemia characterized by the accumulation of abnormal white blood cells in the bone marrow and blood resulting in anemia, susceptibility to infections, bleeding, and hemorrhaging. Twenty to 30 percent of patients receiving the standard treatment (all-trans retinoic acid usually in combination with an anthracycline) suffer relapse. Arsenic trioxide, marketed as Trisenox® by Cephalon, was approved by the FDA in 2000 as a second line of treatment in APL.

Clolar® (clofarabine) is marketed by Genzyme in the US, and by Bioenvision -- a subsidiary of Genzyme -- as the anticancer drug Evoltra® in Europe. Clofarabine, which is approved for refractory or recurring acute lymphoblastic leukemia, and is in clinical development for the treatment of several other cancers, is a nucleoside analog that inhibits DNA synthesis and repair. It also disrupts the integrity of the mitochondrial membrane, leading to programmed cell death of cancer cells. Clofarabine was rationally designed to retain anticancer activity while reducing the neurotoxicity associated with drugs of its class. It is jointly owned by Memorial Sloan-Kettering and the Southern Research Institute.

Hairy Cell Leukemia (HCL) is a rare, indolent leukemia whose name derives from the characteristic appearance of the cytoplasmic projections of the malignant lymphocytes. About 600 people are diagnosed with HCL each year in the United States. Memorial Sloan-Kettering scientists discovered certain antigenic markers that are characteristic of HCL. Marketed by BD Biosciences, these markers, known as CD22 and CD11c, are used in diagnostic tests for the disease.

A small percentage of patients with certain cancers (including cancers of the lung, breast, uterus, and ovary, as well as non-Hodgkin's lymphoma) have seemingly unrelated neurologic symptoms generally referred to as paraneoplastic neurologic syndromes. Symptoms include ataxia of the limbs and trunk, involuntary eye movements, and difficulty with speech articulation, all of which are consistent with the degradation of the cerebellum. Doctors believe this is an autoimmune disease in which patients produce antibodies against antigens expressed on the surface of both the tumor cells and selected cells in the cerebellum. Memorial Sloan-Kettering scientists identified several of these antigens and used them to create diagnostic tests for the syndromes. These tests are marketed by Athena Diagnostics.