Cancer and Oncology Research
Our focus in Oncology Research at Wyeth is to deliver to the oncology clinics innovative new drugs that will change cancer from a life-threatening diagnosis to a disease with which patients can survive and even thrive. This goal can only be achieved through strategic partnerships with academic and clinical research organizations. Now more than ever, we view the cultivation of these shared-risk/shared-reward collaborations with basic scientists, clinicians, and our colleagues in both small and large pharmaceutical companies as crucial to the development of drugs that dramatically change current treatment paradigms for the 'big four' cancers of the breast, prostate, lung, and colon, as well as the less common, but no less life-threatening malignant diseases. We all share the vision that cancer should be a disease that patients can live with, rather than a death sentence, and the scientists in Wyeth Oncology Research, together with our partners elsewhere, are wholly committed to achieving a leadership role in defeating cancer in our lifetimes.
DNA Damage Response Mechanisms
The broad goal of this programme is to identify and develop anticancer agents targeting proteins involved in either the detection or repair of damaged DNA in cancer cells. The broad hypothesis that underlies this group's drug development strategy is that cancer cell proliferation under suboptimal environmental conditions or in the presence of cytotoxic chemotherapy places the cells under persistent genotoxic stress and renders them more sensitive to therapeutic disruption of the cell-cycle checkpoint and DNA repair machineries. The drug development efforts of this group are aimed toward the discovery of a new generation of molecularly-targeted cytotoxic agents.
Tumour-Associated Stress Signaling
The members of this program seek to capitalize on recent advances in our understanding of the signaling pathways and response mechanisms used by cancer cells to circumvent stress-induced cell senescence or lethality. The fact that many of these stress-response pathways are not mutated in cancer cells supports the hypothesis that the acquired dependence of these cells on stress-induced survival pathways can be exploited for the development of a novel class of molecularly targeted anticancer drugs.
Tumour-Host Interactions
This programme works at the interface between the tumour mass and the surrounding host tissue. This research Group aims to develop small molecule and biological drugs that disrupt the lines of communication between the host and the tumour microenvironment. A key facet of this research strategy is the development and implementation of in vitro and in vivo models that more closely recapitulate the biology of tumour development in human patients. The goals of this program are to develop novel drugs that interfere with tumour cell proliferation and migration, as well as tumour-associated angiogenesis.
Tumour Metabolism and Bioenergetics
This programme retains a long-standing focus on the phosphoinositide 3- kinase - mTOR pathway, an oncogenic signaling cascade that is deregulated in virtually all types of cancer cells. Based on these recent insights, the Group has broadened its objectives, and now seeks to develop novel anticancer agents that further exploit the abnormal mechanisms whereby cancer cells produce the metabolic energy that drives tumour cell mass accumulation and cell cycle progression. A key area of investigation is glucose metabolism, which in normal cells relies heavily on mitochondria-dependent oxygen consumption to produce ATP. In contrast, cancer cells are far less dependent on the mitochondria for energy production, and instead metabolize glucose mainly through the glycolytic pathway, a less energy-efficient but considerably more rapid mechanism of ATP production. The molecular alterations that underlie this abnormal shift toward glycolytic metabolism are just now coming to light, unveiling a novel set of potential drug targets for this Group of cancer researchers.
Tumour-Targeted Biotherapy
Therapeutic antibodies, such as Herceptin®, have established themselves as major players in the oncology clinic. While naked antibodies like Herceptin® have at least partially delivered on the magic bullet premise, our Tumor-Targeted Biotherapy Group has focused on enhancing the production of conjugated antibodies that carry a therapeutic payload to tumour cells. Wyeth now has a clinically approved immunoconjugate, Mylotarg®, which is used in the treatment of acute myelogenous leukemia. Several additional calicheamicin-antibody immunoconjugates are in preclinical or clinical development. This Group is currently investigating other types of tumour targeting bio-scaffolds, including the small modular immunopharmaceuticals (SMIPs; developed in partnership with Trubion) and other non-antibody related proteins.