Tumor cell proliferation and survival pathways

Tumor cell proliferation and survival pathways represent the integrated signaling networks that drive the uncontrolled growth and resistance to cell death characteristic of cancer cells [1]. These pathways, most notably the Mitogen-Activated Protein Kinase (MAPK)/ERK and Phosphoinositide 3-kinase (PI3K)/AKT/mTOR cascades, are frequently hijacked in cancer through genetic mutations or overexpression of upstream receptors [2]. By integrating extracellular signals, these pathways regulate the expression of cyclins and anti-apoptotic proteins, such as BCL-2, allowing cancer cells to bypass cell cycle checkpoints and evade programmed cell death [3]. Therapeutic intervention typically involves small-molecule inhibitors or monoclonal antibodies that target specific nodes within these pathways, such as BRAF, MEK, or mTOR [4]. Despite the success of these targeted therapies, the inherent redundancy and crosstalk between pathways often lead to the development of compensatory signaling and drug resistance [5]. Consequently, modern oncology increasingly focuses on combination strategies to simultaneously block multiple points within these survival networks [5]. References: [1] Hanahan D, Weinberg RA. Cell. 2011;144(5):646-74. [2] Sever R, Brugge JS. Cold Spring Harb Perspect Med. 2015;5(4):a006098. [3] Evan GI, Vousden KH. Nature. 2001;411(6835):342-8. [4] Hyman DM, et al. Cell. 2017;168(4):584-599. [5] Holohan C, et al. Nat Rev Cancer. 2013;13(10):714-26.

Other names

Oncogenic signaling pathwaysCancer cell survival signalingPro-proliferative signaling networksTumor growth pathways

Inhibition of intracellular signaling nodes (e.g., kinases, receptors) to block mitogenic signals and restore apoptotic sensitivity [Sever & Brugge, 2015; Hanahan & Weinberg, 2011].