Standard first-line treatment for inoperable locally advanced stage NSCLC is concurrent polychemotherapy with fractionated radiation (60 Gy in 2 Gy fractions) ( 1). Treatment for NSCLC consists of surgical resection, chemotherapy, radiation, targeted therapy, immune therapy, and/or combinations thereof. NSCLC can be further categorized into, generally, adenocarcinoma (AC 40%), squamous cell carcinoma (SQCC 25–30%), large cell undifferentiated carcinoma (10–15%), mixed subtypes (adenosquamous), and the far less common sarcomatoid carcinoma. Lung cancer can be divided into two main categories: non-small cell lung cancer (NSCLC) accounting for 85% of lung cancers, and small cell lung cancer (~15%). The lack of early diagnostic techniques and the intrinsic and/or acquired treatment resistance leading to relapse are major obstacles in finding a cure for lung cancer. More than two thirds of lung cancer patients are diagnosed at an advance stage (III–IV). Lung cancer is the second most commonly diagnosed type of cancer and the leading cause of cancer-related mortality. Here, we focus on the NOTCH signaling pathway, which has a role in stem cell maintenance in non-squamous non-small lung cancer, and we critically assess the potential for targeting the NOTCH pathway to overcome resistance to chemotherapeutic and targeted agents using both preclinical and clinical evidence.Īccording to the World Health Organization, in 2015, every 3.5 s a person died of cancer and one out of five deaths was due to lung cancer. Stem cell pathways are frequently deregulated in cancer and are implicated in recurrence after treatment. CSCs have been identified in NSCLC and have been associated with chemo- and radiotherapy resistance. This tumor heterogeneity is driven by subpopulations of tumor cells termed cancer stem cells (CSCs) that have tumor-initiating capabilities, are highly self-renewing, and retain the ability for multi-lineage differentiation. It has become evident that tumors are composed of a heterogeneous population of cells with different genetic, epigenetic, and phenotypic characteristics that result in diverse responses to therapy, and underlies the emergence of resistant clones. Cell intrinsic mechanisms of resistance include changes in the expression of drug transporters, activation of pro-survival, and anti-apoptotic pathways, as well as non-intrinsic influences of the tumor microenvironment.
Updated by Ritwik Mitra: There aren't many life simulator games that are as fun as The Sims.
To see the best mods to make The Sims 4 even more realistic, keep reading! Some of these are just for cosmetic purposes, some add silly fun, and some make your game even more realistic.
Luckily, the Sims community is full of talented people that create custom hairstyles, clothing, furniture, and even gameplay tweaks. While the game has a ton of content for players, there are some players that still like to get a little more out of their game. Between the base game and the additional Stuff Packs, Expansion Packs, and Game Packs that have been released to add even more content and more fun for players, it's basically impossible to get bored while enjoying a game of The Sims 4. The Sims 4 has so much to do in the game.