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lung_cancer

Lung cancer

Epidemiology

The lungs are the most common source of cerebral metastases and these are usually multiple. The lung primary may be so small as torender it occult.

Necropsy demonstrates cerebral metastases in up to 50 % of patients with small cell lung cancer and non squamous, non small cell lung cancer 1).

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 2).

Classification

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 3).

Complications

1)
Figlin RA, Piantadosi S, Feld R; Lung Cancer Study Group. Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small-cell lung cancer. N Engl J Med. 1988 May 19;318(20):1300-5. PubMed PMID: 2834646.
2)
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.
3)
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: 2018/03/25 14:10 by administrador