A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland neoplasm with a poor long-term prognosis due to multiple recurrences and distant metastatic spread. Circulating tumour cells (CTCs) are tumour cells shed from a primary, recurrent, or metastatic cancer that are detectable in the blood or lymphatics. There is no literature to date confirming the presence of CTCs in ACC. The aim of this study was to determine whether CTCs are detectable in ACC. Blood samples were collected from eight patients with histologically confirmed ACC. The TNM stage of the tumour was recorded, as well as any prior treatment. CTCs were isolated by spiral microfluidics and detected by immunofluorescence staining. Three of the eight patients recruited (32.5%) had staining consistent with the presence of CTCs. Of these three patients with detectable CTCs, one had confirmed pulmonary metastasis, one had suspected pulmonary metastasis and was awaiting confirmation, and one had local recurrence confirmed on re-resection. One patient with known isolated pulmonary metastasis had previously undergone a lung metastasectomy and did not have CTCs detected. CTCs are detectable in ACC. In this small patient sample, CTCs were found to be present in those patients with recurrent local disease and known distant metastatic disease. CTCs in ACC should be investigated further for their potential use as an adjunct in staging, prognosis, and the detection of recurrence.

Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition.

The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.