next-generation-sequencing-for-detection-actionable-mutations-solid

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

As our understanding of the driver mutations necessary for initiation and progression of cancers improves, we gain critical information on how specific ...

Perelman School of Medicine, University of Pennsylvania

Abramson Cancer Center

This review highlights the cutaneous side effects associated with the administration of chemotherapy and discusses the management of these conditions. Rapidly growing cells are the targets of chemotherapy, so the skin, hair follicles, and nail matrix are frequently affected by chemotherapy. Chemotherapy skin reactions are more likely toxic than allergic reactions. The most common cutaneous reactions are alopecia, hyperpigmentation, hand--foot syndrome, radiation recall, hypersensitivity, extravasation injuries, and nail dystrophies. While these side effects are generally not life threatening, they can be a source of significant distress to patients, especially alopecia.

Cutaneous toxicities of cancer therapy.

Thymic neuroendocrine tumor presenting with the ectopic ACTH syndrome.

Testing for somatic alterations, including anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements and epidermal growth factor receptor gene (EGFR) mutations, is standard practice in the diagnostic evaluation and therapeutic management of non-small cell lung cancer (NSCLC), where the results of such tests can predict response to targeted-therapy. ALK rearrangements, EGFR mutations and mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) are considered mutually exclusive in NSCLC. Herein we identified a KRAS Q22K mutation and frameshift mutations in the genes encoding serine/threonine kinase 11 (STK11) and ataxia telangiectasia mutated serine/threonine kinase (ATM) by next-generation sequencing in a patient with ALK rearrangement-positive oligo-metastatic NSCLC, whose disease progressed while on two ALK-targeted therapies. Such a complex diagnostic genetic profile has not been reported in ALK fusion-positive NSCLC. This case highlights the utility of comprehensive molecular testing in the diagnosis of NSCLC.

Rare Complex Mutational Profile in an ALK Inhibitor-resistant Non-small Cell Lung Cancer.

"In situ vaccination" using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient's immune system.

Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy.

The expanding number of targeted therapeutics for non-small cell lung cancer (NSCLC) necessitates real-time tumor genotyping, yet tissue biopsies are difficult to perform serially and often yield inadequate DNA for next-generation sequencing (NGS). We evaluated the feasibility of using cell-free circulating tumor DNA (ctDNA) NGS as a complement or alternative to tissue NGS.

Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next generation sequencing of cell-free circulating tumor DNA.

Article	Year
Cutaneous toxicities of cancer therapy. Current opinion in oncology\| PubMed ID: 11880713	2002
Thymic neuroendocrine tumor presenting with the ectopic ACTH syndrome. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer\| PubMed ID: 23676563	2013
Rare Complex Mutational Profile in an ALK Inhibitor-resistant Non-small Cell Lung Cancer. Anticancer research\| PubMed ID: 25964588	2015
Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 26968202	2016
Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next generation sequencing of cell-free circulating tumor DNA. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 27601595	2016

Evan Alley

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