Annals of Oncology 2008 19(9):1517; doi:10.1093/annonc/mdn600
© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
in this issue
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Matrix metalloproteinase expression and breast cancer outcomes
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Matrix metalloproteinases (MMPs) have been implicated in cancer
invasion and metastasis. Consequently, several MMPs have been
investigated for potential prognostic value as well as targets
for antimetastatic therapy. In this issue, McGowan and Duffy
[p. 1566] report the results of a study that aimed to use a
publicly available database to relate messenger RNA expression
levels for 17 different MMPs to tumor characteristics and outcomes
in patients with breast cancer. Considering expression of 17
MMPs, these authors report that only MMP-1 was significantly
increased in tumors >2 cm in size compared with those
2 cm
while MMP-1, -9, -12 and -15 were significantly elevated in
high-grade compared with low-grade tumors. These authors suggest
that their results when combined with previously published preclinical
data suggest that MMP-1, -12, -14 and -15 are involved in breast
tumor progression.
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Intensive induction chemoradiotherapy plus maintenance gemcitabine vs. gemcitabine alone for pancreatic cancer
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The prognosis for locally advanced pancreatic cancer (LAPC),
which accounts for 29% of initial cases, lies between those
for metastatic and resected disease. However, the role of chemoradiation
with systemic chemotherapy compared with chemotherapy alone
in locally advanced pancreatic cancer (LAPC) is uncertain. In
this issue, Chauffert et al. [p. 1592] report the definitive
results of a phase III trial that aimed to compar intensive
induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent
cisplatin) followed by maintenance gemcitabine with gemcitabine
alone for patients with unresectable LAPC. These authors report
that the intensive induction schedule of chemoradiotherapy was
more toxic and less effective than gemcitabine alone. They suggest
that in future trials, the timing of chemoradiotherapy must
be explored as one possibility could be to use it only in subgroups
of patients whose tumors have not spread and are well controlled
by initial chemotherapy.
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cMET expression in NSCLC patients treated with EGFR tyrosine kinase inhibitors
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The epidermal growth factor receptor tyrosine kinase inhibitors
(EGFR-TKIs), gefitinib and erlotinib have demonstrated activity
in approximately 10% of unselected non-small-cell lung cancer
(NSCLC) patients. The cMET tyrosine kinase receptor, normally
expressed by epithelial cells, is overexpressed and amplified
in a variety of human tumors, including NSCLC.
cMET stimulation
induces specific phosphorylation of several tyrosine residues
which, in turn, activate multiple downstream signaling pathways,
including the RAS/ERK, PI3K/AKT, and cSRC kinase pathways. Engelman
et al. reported that cMET amplification induced resistance to
gefitinib in a gefitinib-sensitive lung cancer cell line. Moreover,
cMET inhibition with a cMET tyrosine kinase inhibitor (PHA-665,752)
restored gefitinib sensitivity. In this issue, Zucali et al.
[p. 1605] report the results of a study that aimed to investigate
tumor samples of EGFR-TKI-treated NSCLC patients for potential
biological markers of intrinsic EGFR-TKI resistance, especially
related to epithelial–mesenchymal transition. These authors
conclude that activated cMET[pY1003] appears to be a marker
of primary gefitinib resistance in NSCLC patients.
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Palifermin for the prevention of high-dose methotrexate-induced oral mucositis
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Oral mucositis and myelosuppression represent dose-limiting
toxicity effects of high-dose methotrexate-based chemotherapy.
Mucositis is associated with an increased risk of life-threatening
infections with the need for total parenteral nutrition, i.v.
analgetic therapy, and may lengthen hospital stay with increased
economic burden and consumption of health care resources. Numerous
substances have been used in addition to treat oral mucositis
such as ice chips, antioxidants as glutamine,
N-acetylcysteine,
benzydamine hydrochloride and antiinflammatory agents like prostaglandine
E1 and E2, but none of them has proven an unequivocal clinical
benefit. Palifermin is a recombinant human keratinocyte growth
factor (KGF) which is known to stimulate growth of epithelial
cells in a wide variety of tissues. The guidelines of the Multinational
Association of Supportive Care in Cancer recommend the use of
palifermin in patients who are receiving high-dose chemotherapy
and total body irradiation with autologous stem-cell transplantation.
In this issue, Schmidt et al. [p. 1644] describe the effects
of palifermin in patients treated within the GMALL-B-ALL 2002
protocol containing high-dose methotreaxate who developed a
severe mucositis in cycle A1/B1.
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Quote
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‘To say, for example that a man is made of certain chemical
elements is a satisfactory description only for those who intend
to use him as fertilizer.’
Nobel laureate and geneticist H. J. Muller in Science and Criticism
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