Cancer Signaling Pathways and Targeted Therapy

Explore the steps of tumorigenesis, from mutations and immune surveillance evasion to dormancy and the angiogenic switch, basement membrane invasion, and lymphatic metastasis, with links to targeted therapy.

Explore how normal cells use insulin and growth factor signaling via receptors, plus paracrine and autocrine cues, and how cancer cells hijack these pathways.

Explore EGFR signaling with ligand binding, dimerization, tyrosine kinase activation, and cancer-promoting mutations, and examine how targeted therapies confront amplification, truncation, and intracellular mutations plus resistance.

Examine EGFR targeted therapy across non-small cell lung cancer and colorectal cancer, detailing erlotinib's inhibition, resistance mutations, and the progression from first to third generation inhibitors, including cetuximab endocytosis.

Explore the MAPK pathway, detailing G12C mutated Ras and BRAF V600E mutations, selective inhibitors Dabrafenib and Trametinib, resistance, and colorectal cancer exceptions, with downstream MEK and CDK4/6 targets.

Explore the PI3K/Akt/mTOR mechanism: activation by receptor tyrosine kinases or Ras, PIP2 to PIP3, and PDK1 docking, promoting cell survival, translation, and glycogen synthesis, with PTEN counteracting.

Explore the clinical PI3K-AKT-mTOR pathway in cancer, highlighting copanlisib in follicular lymphoma, PIK3CA-driven breast cancer, and resistance mechanisms shaping estrogen receptor targeted therapy.

Explore the TGF-beta Smad pathway from ligand activation to Smad-mediated transcription. Examine non-canonical Erk activation, cancer-specific roles, and car-t strategies using dominant negative TGF beta receptor two.

Explore the canonical and noncanonical NF kappa B signaling pathways, regulators like I kappa B and I kappa B kinase, and proteasomal degradation activating inflammatory gene transcription in cancer.

Explore the canonical Wnt beta-catenin pathway from wingless ligands and frizzled receptors through the destruction complex to beta-catenin–TCF transcription, highlighting mutations and cancer implications.

Explore how cancer cells evade immunity by PD-L1/PD-1 interactions and how immune checkpoint blockade with antibodies restores T cell activity, highlighting neoantigens and MHC I presentation.

Examine factors shaping immune checkpoint inhibitor efficacy, including neoantigen load, DNA repair mutations, mutational burden, PD-L1 levels, and tumor infiltration (hot, cold, desert), with clinical outcomes and pembrolizumab trials.

Explore the ALK receptor, a proto-oncogene with EML4-ALK fusions driving non-small cell lung cancer, anaplastic large cell lymphoma, and neuroblastoma, and how inhibitors address central nervous system relapse and resistance.

Explore the fibroblast growth factor receptor (FGFR) biology, its amplifications, mutations, and fusions, and the signaling pathways (MAPK/ERK, PI3K-AKT, JAK-STAT, PLC gamma) driving cancer and targeted therapies.