Possible application of circulating free tumor DNA in non-small cell lung cancer patients.

Liquid biopsies have been heralded as a game changer in cancer management. Blood tests offer a minimally invasive, safe and sensitive complementary (or even alternative) approach for tissue biopsies. With lung cancer being the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide, due to the limitations of tissue sampling, liquid biopsies must urgently materialize in the clinic. In this short review, we will present the current applications of cell-free DNA (cfDNA) in lung cancer management, emphasizing on our own experience and previous work. We will also shortly comment on the challenges and need for a coordinated collaboration combining disciplines and sectors (from academia to health economies) in order to accelerate liquid biopsy development in lung cancer and other cancers.

Anaplastic lymphoma kinase inhibitors in phase I and phase II clinical trials for non-small cell lung cancer.

INTRODUCTION: Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development. Areas covered: This review will focus on new ALK inhibitors, currently in phase 1 or 2 clinical studies. We will also comment on the mechanisms of resistance to ALK inhibition and the strategies to delay or overcome resistance. Expert opinion: The therapeutic management of ALK-rearranged NSCLC has been greatly improved. Next-generation ALK inhibitors have shown differential potency against ALK rearrangements and ALK resistance mutations. The molecular profile of the tumor at the time of disease progression to crizotinib is crucial for the sequencing of novel ALK TKIs. Ongoing clinical studies will address key issues, including the optimal therapeutic algorithm and whether combinational approaches are more effective than single ALK inhibition for the outcome of ALK-rearranged NSCLC patients.

Pharmacological management of relapsed/refractory NSCLC with chemical drugs.

INTRODUCTION: Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach. Areas covered: In this review we are discussing the current treatment of relapsed or refractory lung cancer. We have thoroughly searched the literature (Pubmed) the last five years for studies or reviews published on the issue of second-line therapy in lung cancer using as key words, lung cancer, relapse, EGFR mutations, ALK rearrangements, chemotherapy and immunotherapy Expert opinion: The prognosis of lung cancer has been radically improved. Due to the recent development of checkpoint inhibitors, this also occurs for patients whose tumor's are not driven by a genetic alteration and who, until recently, derived only minimal benefit from chemotherapy.

HER3 as a Therapeutic Target in Cancer.

Targeting members of the human epidermal growth factor receptor family, especially EGFR and HER2, has been an established strategy for the treatment of tumors with abnormally activated receptors due to overexpression, mutation, ligand-dependent receptor dimerization and ligand-independent activation. Less attention has been paid to the oncogenic activity of HER3, although there is growing evidence that it mediates resistance to EGFR and HER2 pathway directed therapies. The main caveat for the development of effective HER3 targeted therapies is the absence of a strong enzymatic activity to target, as well as the limited potential for single-agent activity. In this review, we highlight the role of HER3 in cancer and, more specifically, in lung cancer. The basis for HER3 involvement in HER2 resistance and EGFR inhibition is discussed, as well as current pharmacologic strategies to combat HER3 inhibition.

Outcome of patients treated with palliative weekly paclitaxel plus cetuximab in recurrent head and neck cancer after failure of platinum-based therapy.

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.