Personalized Medicine for Targeted and Platinum-Based Chemotherapy of Lung and Bladder Cancer

Abstract

The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications.

Targeting glycogen metabolism in bladder cancer

“…72–76 In patients with viscerally metastatic bladder cancer, the current standard of treatment is platinum-based chemotherapy, with a median survival after treatment of approximately 1 year. 77 Although our studies have demonstrated that AGL is a prognostic marker in bladder cancer, 31 whether AGL levels can predict responses to various treatments has not yet been tested.…”

Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

“…The levels of such adducts are the result of numerous factors that govern cellular responses to drug exposure including genetics, tumor microenvironment, kidney function, overall patient health and others (13). The key challenge of this approach is the need to dose patients with full-dose chemotherapy in order to recover enough analyte to accurately quantify extremely low levels of drug-DNA adducts (14). Furthermore, therapeutic dosing is a poor diagnostics strategy and puts patients at risk.…”

Alternative therapies in patients with non-muscle invasive bladder cancer

“…Additional tools are needed for optimizing the treatment and human genome is probably the most valuable source for this purpose. Van Allen et al [55] showed that ERCC2 (a nucleotide excision repair gene) mutation detected by whole-exome sequencing is associated with cisplatin response. Similarly, ERCC1, BRCA1, P53 were found to be useful for the prediction of sensitivity to cisplatin; whereas hENT1 and RRM1 are reported as beneficial for GEM.…”