Molecular Oncology of Bladder Cancer from Inception to Modern Perspective

Abstract

Within the last forty years, seminal contributions have been made in the areas of bladder cancer (BC) biology, driver genes, molecular profiling, biomarkers, and therapeutic targets for improving personalized patient care. This overview includes seminal discoveries and advances in the molecular oncology of BC. Starting with the concept of divergent molecular pathways for the development of low- and high-grade bladder tumors, field cancerization versus clonality of bladder tumors, cancer driver genes/mutations, genetic polymorphisms, and bacillus Calmette-Guérin (BCG) as an early form of immunotherapy are some of the conceptual contributions towards improving patient care. Although beginning with a promise of predicting prognosis and individualizing treatments, “-omic” approaches and molecular subtypes have revealed the importance of BC stem cells, lineage plasticity, and intra-tumor heterogeneity as the next frontiers for realizing individualized patient care. Along with urine as the optimal non-invasive liquid biopsy, BC is at the forefront of the biomarker field. If the goal is to reduce the number of cystoscopies but not to replace them for monitoring recurrence and asymptomatic microscopic hematuria, a BC marker may reach clinical acceptance. As advances in the molecular oncology of BC continue, the next twenty-five years should significantly advance personalized care for BC patients.

Novel immunotherapy in the management of advanced urothelial cancer - review of the literature

“…Therefore, there is such a great and pressing need for a thorough examination and qualification of the pathological basis of bladder neoplasms. Looking at the disorders of the genome of neoplastic cells, we distinguish between low-risk and high-risk cancers, low-grade cancers are distinguished by genome and mutation stability, while high-grade genome instability and numerous changes predisposing malignancy are distinguished (16). In low-grade tumors, the basic genome change turns out to be FGFR3 gene mutations and epithelial hyperplasia, while in high-grade tumors, TP53 changes and epithelial dysplasia, which gives a dualistic division and directly affects the targeting of therapy depending on the pathological characteristics of the tumor (17).…”

Multi‐Targeted and On‐Demand Non‐Coding RNA Regulation Nanoplatform against Metastasis and Recurrence of Triple‐Negative Breast Cancer

“…3) Nuclear target. After entering tumor cells, MTOR is subjected to lysosomal hyaluronidase-induced shell (HPU) detachment, [23,24] leading to a TAT peptide exposed nano-core, thus increasing the delivery of pa21-p205 into the nucleus of TNBC cells and BrCSCs. [25,26] Considering the advanced features mentioned above, our MTOR offers a new strategy against metastasis and recurrence of TNBC.…”

Untargeted urinary metabolomics for bladder cancer biomarker screening with ultrahigh-resolution mass spectrometry

“…MS, compared to NMR, detects far wider variety of molecules with much greater sensitivity, resolution, and accuracy using much less material 11 . During the last fteen years, metabolomic analytical approaches have been extensively employed to explore BC and nd possible biomarkers in urine, serum, and tissues 4,5,12,13 . Compared to serum and tissue, urine metabolomics may be affected by dilution factor, but urine is more available than tissue or serum, and the procedure non-invasive.…”