Apoptosis and cancer chemotherapy

  title={Apoptosis and cancer chemotherapy},
  author={Guy W.J. Makin and John A. Hickman},
  journal={Cell and Tissue Research},
Abstract Apoptosis is a fundamental mechanism of cell death that can be engaged by a range of cellular insults. One of the major modes of action of chemotherapeutic drugs may be via the activation of apoptosis. Understanding how the cell death program is engaged following an insult, and hence why it fails to be engaged in certain settings, offers a novel approach to overcoming the clinical problem of drug resistance. The tumour suppressor gene p53 and its downstream effector genes p21, mdm-2… 

2 Resistance to Apoptosis in Cancer Therapy

A major challenge for the immediate future is to validate the concept that apoptosis plays a crucial role in tumor response to therapy in patients receiving conventional and “designer” drugs, and more specifically, to confirm that the latter effectively hit their targets and produce the desired biological responses.

The Intrinsic Pathway of Apoptosis

In this chapter, the various components of the intrinsic pathway are reviewed, alterations in this pathway in various cancers are described, and evidence that some of these same antiapoptotic alterations might contribute to anticancer drug resistance under certain circumstances is discussed.

Apoptosis and Molecular Targeting Therapy in Cancer

The main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells are provided and how carcinogenesis could be developed via defective apoptotic pathways or their convergence is discussed.

BMX Negatively Regulates BAK Function, Thereby Increasing Apoptotic Resistance to Chemotherapeutic Drugs.

The finding that BMX directly inhibits a core component of the intrinsic apoptosis machinery opens opportunities to improve the efficacy of existing chemotherapy by potentiating BAK-driven cell death in cancer cells.

Apoptosis: programmed cell death at a molecular level.

How deregulation of apoptosis may contribute to autoimmunity, cancer, and neurodegenerative disorders and strategies some viruses have evolved that interfere with the host's apoptotic pathways are described.

Implication for Cancer Specific Therapy Inhibitor of Apoptosis Proteins in Human Tumor Cells : Coexistence of High Levels of Apoptotic Signaling and Updated

The results suggest that upregulated IAP expression counteracts the high basal caspase-3 activity observed in these tumor cells and that apoptosis in tumor cells but not normal cells can be induced by blocking IAP activity.



Apoptosis and chemotherapy resistance.

Apoptosis , p 53 , and Tumor Cell Sensitivity to Anticancer Agents 1

This review finds that wild-typep53predisposes cells to a more rapid rate of cell death after DNA damage, particularly with normal or minimally transformed cells, that short-term assays have led to the conclusion that mutations in p53 confer resistance to genotoxic agents.

Epigenetic determinants of resistance to etoposide regulation of Bcl-X(L) and Bax by tumor microenvironmental factors.

Microenvironmental factors reduce the sensitivity of a B-cell lymphoma to etoposide in vitro by modulating the expression and functions of Bax and Bcl-x(L), which may provide a paradigm for epigenetically induced drug resistance in other tumors.

A model for p53-induced apoptosis

Examination of transcripts induced by p53 expression before the onset of apoptosis stimulated additional biochemical and pharmacological experiments suggesting that p53 results in apoptosis through a three-step process: the transcriptional induction of redox-related genes; the formation of reactive oxygen species; and the oxidative degradation of mitochondrial components, culminating in cell death.

Does Apoptosis Contribute to Tumor Cell Sensitivity to Anticancer Agents

If clonogenic survival is used to assess cell killing, and real tumor cells are used, then apoptosis, and the genes controlling it, play little or no role in the sensitivity of tumor cells of nonhematological origin to anticancer drugs and radiation.

Drug-target interactions: only the first step in the commitment to a programmed cell death?

It is argued that it is possible that the outcome of chemotherapy may be determined by the response of the cell to the formation of the drug-target complex, and/or its sequellae, rather than to the biochemical changes brought about by the drug alone.

Bax suppresses tumorigenesis and stimulates apoptosis in vivo

It is shown that p53-dependent expression of bax is induced in slow-growing apoptotic tumours, and this is the first demonstration that Bax acts as a tumour suppressor, and the findings indicate that bax could be a component of the p 53-mediated apoptotic response in this system.