Molecular mechanisms of anti-cancer treatment resistance in prostate tumours
Authors:
M. Raudenská 1; J. Balvan 1; J. Gumulec 1; M. Sztalmachová 1; H. Polanská 1; V. Adam 2; M. Stiborová 3; T. Eckschlager 4; R. Kizek 2; M. Masařík 1
Authors place of work:
Masarykova univerzita, Brno
Lékařská fakulta
Ústav patologické fyziologie
Přednostka: prof. MUDr. Anna Vašků, CSc.
1; Mendelova univerzita v Brně
Ústav chemie a biochemie
Vedoucí: doc. RNDr. Vojtěch Adam, Ph. D.
2; Univerzita Karlova, Praha
Přírodovědecká fakulta
Katedra biochemie
Vedoucí: doc. RNDr. Miroslav Šulc, Ph. D.
3; 2. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Motol
Klinika dětské hematologie a onkologie
Přednosta: prof. MUDr. Jan Starý, DrSc.
4
Published in the journal:
Prakt. Lék. 2014; 94(2): 88-93
Category:
Of different specialties
Summary
There are few problems more frustrating and depressing to oncologists and cancer patients alike than anti-cancer have treatment resistance. It comes in two varieties: primary and acquired. More and more cancers become responsive to newly developed therapies that are successful in inducing responses in cancers previously considered intrinsically resistant, and the emphasis gradually moves on more and more problematic acquired types of resistance. Acquired resistance may arise through many types of mechanisms. One of them is a constitutive activation of NF-κB, which has been described in a great number of solid tumours and this activation appears to support cancer cell survival and to reduce the sensitivity against chemotherapeutic drugs. Additionally, some anticancer therapies induce this transcription factor themselves and through this mechanism lower their own efficiency. In some cases, a first cycle of an anti-cancer treatment may select resistant population of tumour cells that subsequently leads to recurrence of disease and to the failure of treatment. This may be particularly true for tumours that are composed of a heterogeneous population of cells, which is exactly the case of prostate tumours. Tumour progression needs a positive and reciprocal feedback between cancer associated fibroblasts (CAFs) and cancer cells. Cancer cells induce and maintain the fibroblasts activated phenotype (activated transcription of certain genes), which produce a series of growth factors and cytokines that sustain tumour progression by promoting extracellular matrix (ECM) remodelling, cell proliferation, angiogenesis and epithelial-mesenchymal transition (EMT). A thorough understanding of chemoresistance pathways and how they interact would facilitate two important outcomes. Firstly, identifying patients who will not benefit from chemotherapy prior to their exposure will avoid unnecessary toxicity and allow them to move on to alternative treatment options. Secondly, targets for further drug development may also arise.
Keywords:
anti-androgen resistance – signal pathways – mechanisms of chemoresistance – radioresistance – metallothionein – NF-κB – PTEN – p53 – cancer associated fibroblasts (CAFs)
Zdroje
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