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Lung cancer

Lung cancer is the leading cause of cancer mortality worldwide, accounting for 1.38 million annual deaths, representing 18.2% of total deaths from cancer 1).

see Non small cell lung cancer.

see Small cell lung cancer.

see Brain metastases from lung cancer.

Diagnosis

A lung lesion should be biopsied to rule out SCLC before obtaining tissue from the cerebral mass.

PET Scan can detect small malignancies.

Useful in NSCLC.

Not useful in initial evaluation of SCLC.

Treatment

Lung cancer treatment remains a challenge for clinical practice and new therapeutic approaches are urgently needed. Loss of functional WEE1 kinase causes DNA replication stress, DNA damage and unscheduled mitotic entry due to elevated CDK activity. The selective WEE1 inhibitor MK-1775 synergize with DNA-damaging agent to inhibit cancer cell growth. Here we report that inhibition of Sirt1 deacetylase through small interfering RNA or selective inhibitor Ex527 greatly enhances MK-1775-induced growth inhibition and apoptosis in human lung cancer cells. We further demonstrate that Sirt1 interacts and deacetylates homologous recombination (HR) repair machinery proteins, including NBS1 and Rad51. Inhibition of Sirt1 impairs HR repair activity, which causes unrepairable damage when combining MK-1775 and Ex527. Meanwhile, combination of MK-1775 and Ex527 induces cooperative antitumor activity in lung cancer xenograft model in vivo. Thus, a study provides a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers 2).

1)
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134. PubMed PMID: 21296855.
2)
Chen G, Zhang B, Xu H, Sun Y, Shi Y, Luo Y, Jia H, Wang F. Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis. Oncogene. 2017 Sep 4. doi: 10.1038/onc.2017.297. [Epub ahead of print] PubMed PMID: 28869605.
lung_cancer.txt · Last modified: 2017/09/29 08:27 by administrador