Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG

Abstract

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000–45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

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Fusobacterium May Help Colorectal Cancer Grow and Spread

Fusobacterium, found in the stomach and intestines, may help fuel the growth of colorectal cancer and metastases. In a mouse model of colorectal cancer, using antibiotics to kill these bacteria slowed tumor growth.

http://ift.tt/2pXs0KQ

Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR/Integrin β1/ Src signaling in triple negative breast cancer cells

Abstract

Autophagy is a catabolic process for degrading dysfunctional proteins and organelles, and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in breast cancer cells is not well understood. In the present study, we investigated the role of autophagy in highly aggressive and metastatic triple negative breast cancer (TNBC) and non-metastatic breast cancer cells and demonstrated that the knockdown of autophagy-related genes (LC3 and Beclin-1) inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration/invasion and induced apoptosis in MDA-MB-231 and BT-549 TNBC cells. Knockdown of LC3 and Beclin-1 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, uPAR/integrin-β1/Src, and PARP1. In conclusion, our study suggests that LC3 and Beclin-1 are required for cell proliferation, survival, migration and invasion, and may contribute to tumor growth and progression of highly aggressive and metastatic TNBC cells and therapeutic targeting of autophagy genes may be a potential therapeutic strategy for TNBC in breast cancer.

http://ift.tt/2CksVrf

Fusobacterium May Help Colorectal Cancer Grow and Spread

Fusobacterium, found in the stomach and intestines, may help fuel the growth of colorectal cancer and metastases. In a mouse model of colorectal cancer, using antibiotics to kill these bacteria slowed tumor growth.

from Cancer via ola Kala on Inoreader http://ift.tt/2pXs0KQ
via IFTTT

Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR/Integrin β1/ Src signaling in triple negative breast cancer cells

Abstract

Autophagy is a catabolic process for degrading dysfunctional proteins and organelles, and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in breast cancer cells is not well understood. In the present study, we investigated the role of autophagy in highly aggressive and metastatic triple negative breast cancer (TNBC) and non-metastatic breast cancer cells and demonstrated that the knockdown of autophagy-related genes (LC3 and Beclin-1) inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration/invasion and induced apoptosis in MDA-MB-231 and BT-549 TNBC cells. Knockdown of LC3 and Beclin-1 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, uPAR/integrin-β1/Src, and PARP1. In conclusion, our study suggests that LC3 and Beclin-1 are required for cell proliferation, survival, migration and invasion, and may contribute to tumor growth and progression of highly aggressive and metastatic TNBC cells and therapeutic targeting of autophagy genes may be a potential therapeutic strategy for TNBC in breast cancer.

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A review on adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in nonsmall cell lung cancer patients

B Biswas, N Ghadyalpatil, MV Krishna, J Deshmukh

Indian Journal of Cancer 2017 54(5):55-64

The epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of EGFR-mutant nonsmall cell lung cancer (NSCLC). These EGFR TKIs demonstrate a different adverse event (AE) profile as compared to conventional chemotherapy agents. They are more commonly associated with cutaneous AEs and diarrhea while hematological AEs occurred commonly with chemotherapy agents. These AEs are the extension of pharmacological effect and occur as a result of blockade of EGFR-regulated pathways in the skin and gastrointestinal tract. This review article sheds light on the safety profile of first-, second-, and third-generation EGFR TKIs based on data obtained from several clinical trials conducted in NSCLC patients and highlights trials comparing these agents with the conventional chemotherapy agents. The strategies to manage EGFR TKI-related AEs are also reviewed.

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Epidermal growth factor receptor mutation testing: From conventional to real-time diagnosis of lung cancer

T Raja, NK Warrier

Indian Journal of Cancer 2017 54(5):9-14

Patients with non-small cell lung cancer (NSCLC) commonly harbor epidermal growth factor receptor (EGFR) mutation. Due to the complex disease pathology, early-stage diagnosis of patients with EGFR mutation is essential to make appropriate treatment decision. Tyrosine kinase inhibitors (TKIs) are commonly used for their treatment, but almost half of the patients with EGFR mutation do not respond to the available TKIs and develop acquired resistance owing to T790M mutation. The presence of T790M mutation also warrants a robust diagnostic method so as to allow clinicians to modify cancer treatment. Numerous diagnostic techniques for the detection of EGFR mutation, however, their performance and working profile variation necessitate a comparative evaluation for the selection of a better diagnostic method or an advanced combination of theirs. The present review compares various EGFR-mutation detection techniques such as Sanger sequencing, next-generation sequencing, and different polymerase chain reaction (PCR)-based methods. It also highlights the role of advanced PCR-based techniques, i.e., real-time or quantitative PCR and digital droplet PCR (ddPCR) for detecting EGFR mutations in NSCLC patients. ddPCR, when compared to other methods, shows enhanced sensitivity, superior reliability, and improved time and cost-effectiveness. Moreover, its ability to detect EGFR mutations including T790M, in both conventional (solid tissue biopsy samples) and nonconventional sample sources (blood, plasma, and urine samples), gives it an edge over other diagnostic techniques and support its integration in clinical practice setting.

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