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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Debate

Clinical observations on chemotherapy curable malignancies: unique genetic events, frozen development and enduring apoptotic potential

Author: Philip Savage

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

A select number of relatively rare metastatic malignancies comprising trophoblast tumours, the rare childhood cancers, germ cells tumours, leukemias and lymphomas have been routinely curable with chemotherapy for more than 30 years. However for the more common metastatic malignancies chemotherapy treatment frequently brings clinical benefits but cure is not expected. Clinically this clear divide in outcome between the tumour types can appear at odds with the classical theories of chemotherapy sensitivity and resistance that include rates of proliferation, genetic development of drug resistance and drug efflux pumps. We have looked at the clinical characteristics of the chemotherapy curable malignancies to see if they have any common factors that could explain this extreme differential sensitivity to chemotherapy.

Discussion

It has previously been noted how the onset of malignancy can leave malignant cells fixed with some key cellular functions remaining frozen at the point in development at which malignant transformation occurred. In the chemotherapy curable malignancies the onset of malignancy is in each case closely linked to one of the unique genetic events of; nuclear fusion for molar pregnancies, choriocarcinoma and placental site trophoblast tumours, gastrulation for the childhood cancers, meiosis for testicular cancer and ovarian germ cell tumours and VDJ rearrangement and somatic hypermutation for acute leukemia and lymphoma. These processes are all linked to natural periods of supra-physiological apoptotic potential and it appears that the malignant cells arising from them usually retain this heightened sensitivity to DNA damage. To investigate this hypothesis we have examined the natural history of the healthy cells during these processes and the chemotherapy sensitivity of malignancies arising before, during and after the events.

Summary

To add to the debate on chemotherapy resistance and sensitivity, we would argue that malignancies can be functionally divided into 2 groups. Firstly those that arise in cells with naturally heightened apoptotic potential as a result of their proximity to the unique genetic events, where the malignancies are generally chemotherapy curable and then the more common malignancies that arise in cells of standard apoptotic potential that are not curable with classical cytotoxic drugs.
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Metadata
Title
Clinical observations on chemotherapy curable malignancies: unique genetic events, frozen development and enduring apoptotic potential
Author
Philip Savage
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1006-6

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

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Genomic profiling of CHEK2*1100delC-mutated breast carcinomas

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Conventional transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for the treatment of hepatocellular carcinoma

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A retrospective chart review of drug treatment patterns and clinical outcomes among patients with metastatic or recurrent soft tissue sarcoma refractory to one or more prior chemotherapy treatments

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Evaluation of an assay for methylated BCAT1 and IKZF1 in plasma for detection of colorectal neoplasia

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Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer

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Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations
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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

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