Treatment of small cell lung cancer

Morabito, Alessandro; Carillio, Guido; Daniele, Gennaro; Piccirillo, Maria Carmela; Montanino, Agnese; Costanzo, Raffaele; Sandomenico, Claudia; Giordano, Pasqualina; Normanno, Nicola; Perrone, Francesco; Rocco, Gaetano; Maïo, Massimo Di

doi:10.1016/j.critrevonc.2014.03.003

Cited by 60 publications

(42 citation statements)

References 76 publications

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“…26 The tyrosine kinase inhibitor sunitinib has also been shown to increase PFS in small cell lung cancer in a phase II randomized trial. 27 Given that small cell lung cancers have high expression of PARP1, PARP inhibition is another attractive strategy. PARP inhibitors are currently being explored in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Natural history and outcome of neuroendocrine carcinoma of the cervix

Margolis

Tergas²,

Chen

et al. 2016

Gynecologic Oncology

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Objective Neuroendocrine carcinomas of the cervix (NECC) are rare and thought to be aggressive. We performed a population-based analysis to examine the natural history, treatment patterns and outcomes of women with NECC compared to squamous cell carcinoma (SCCC) and adenocarcinoma (AC) of the cervix. Methods The National Cancer Database (NCDB) was utilized to identify women with NECC, SCCC, and AC treated from 1998–2011. Clinical, demographic, and treatment characteristics were compared between the groups. The association between tumor histology and survival was examined using Kaplan-Meier analyses and multivariable Cox proportional hazards regression models. Results We identified 127,332 patients, including 1,896 (1.5%) with NECC and 101,240 (79.5%) with SCCC and 24,196 (19.0%) with AC. Patients with NECC were younger, more often white, commercially insured, and diagnosed with metastatic disease at presentation compared to women with SCCC. Patients with early-stage NECC were more likely to receive adjuvant chemotherapy and radiation after surgery (P<0.05 for both). In multivariable models stratified by stage and adjusted for clinical and demographic characteristics, the risk of death was higher for patients with NECC compared to SCCC for all stages of disease: stage IB–IIA (HR=2.96; 95% CI, 2.48–3.52), stage IIB–IVA (HR=1.70; 95% CI, 1.45–1.99) and stage IVB (HR=1.14; 95% CI, 0.91–1.43). Conclusion NECC are aggressive tumors associated with an increased risk of death. Survival is inferior for NECC compared to squamous cell tumors for women with both early and advanced stage disease.

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Section: Discussionmentioning

confidence: 99%

Natural history and outcome of neuroendocrine carcinoma of the cervix

Margolis

Tergas²,

Chen

et al. 2016

Gynecologic Oncology

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“…In addition, cancer cells may develop resistance to the chemotherapeutic agents. Currently, the therapy efficacy can be determined only after a few weeks to several months, which represents one of the major challenges in the timely management of cancer (Morabito et al, 2014; Gottesman et al, 2002). Therefore, there is a need to develop approaches for rapid screening techniques to evaluate the efficacy of anti-cancer drugs on tumours that would help in stratifying patient responders and non-responders early on.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic platform for drug screening in a 3D cancer microenvironment

Pandya

Dhingra

Prabhakar

et al. 2017

Biosensors and Bioelectronics

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Development of resistance to chemotherapy treatments is a major challenge in the battle against cancer. Although a vast repertoire of chemotherapeutics is currently available for treating cancer, a technique for rapidly identifying the right drug based on the chemo-resistivity of the cancer cells is not available and it currently takes weeks to months to evaluate the response of cancer patients to a drug. A sensitive, low-cost diagnostic assay capable of rapidly evaluating the effect of a series of drugs on cancer cells can significantly change the paradigm in cancer treatment management. Integration of microfluidics and electrical sensing modality in a 3D tumour microenvironment may provide a powerful platform to tackle this issue. Here, we report a 3D microfluidic platform that could be potentially used for a real-time deterministic analysis of the success rate of a chemotherapeutic drug in less than 12 h. The platform (66 mm × 50 mm; L×W) is integrated with the microsensors (interdigitated gold electrodes with width and spacing 10 μm) that can measure the change in the electrical response of cancer cells seeded in a 3D extra cellular matrix when a chemotherapeutic drug is flown next to the matrix. B16-F10 mouse melanoma, 4T1 mouse breast cancer, and DU 145 human prostate cancer cells were used as clinical models. The change in impedance magnitude on flowing chemotherapeutics drugs measured at 12 h for drug-susceptible and drug tolerant breast cancer cells compared to control were 50552 ± 144 Ω and 28786 ± 233 Ω, respectively, while that of drug-susceptible melanoma cells were 40197 ± 222 Ω and 4069 ± 79 Ω, respectively. In case of prostate cancer the impedance change between susceptible and resistant cells were 8971 ± 1515 Ω and 3281 ± 429 Ω, respectively, which demonstrated that the microfluidic platform was capable of delineating drug susceptible cells, drug tolerant, and drug resistant cells in less than 12 h.

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“…Most patients initially respond to platinum-based chemotherapy, but usually relapse and acquire chemo-resistant disease3 such that the median overall survival (OS) is 9–12 months and 5-year survival is <5% (ref. 4). Advances with targeted therapies are yet to materialise and chemotherapy regimens have remained unchanged for almost three decades5.…”

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confidence: 99%

Vasculogenic mimicry in small cell lung cancer

et al. 2016

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Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form ‘endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.

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Treatment of small cell lung cancer

Cited by 60 publications

References 76 publications

Natural history and outcome of neuroendocrine carcinoma of the cervix

Natural history and outcome of neuroendocrine carcinoma of the cervix

A microfluidic platform for drug screening in a 3D cancer microenvironment

Vasculogenic mimicry in small cell lung cancer

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