Are we ready for personalized cancer treatments?

I'm not sure this has the potential to become the standard of care anytime soon. However the challenge is there and most likely worth a try.

What are the current limiting factors for this approach?

- Cost (but despite the fact it is so evident, I believe it is not the main one)

- Trial Design for personalized therapies; how can we prove those therapies are effective?

- Facilities, how many cancer centers are TRULY ready to accomodate routine processing and biobanking of primary cell lines or xenograft?

- What's first? Whole exome seq or In Vitro drug response?

Mol Cancer Ther. 2010 Dec 6. [Epub ahead of print]

Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer.

Villarroel MC, Rajesh Kumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, Hruban RH, Eshleman JR, Klein AP, Laheru D, Donehower RC, Hidalgo M.

1GI Oncology, The Sidney Kimmel Cancer Center at Johns Hopkins.

Abstract

Metastasis and drug resistance are the major causes of mortality in patients with pancreatic cancer. Once developed, the progression of pancreatic cancer metastasis is virtually unstoppable with current therapies. Here we report the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA damaging agents, based on the observation of significant activity of this class of drugs against a personalized xenograft generated from the patient's surgically resected tumor. Mitomycin C treatment, selected based on its robust preclinical activity in a personalized xenograft generated from the patient's tumor, resulted in long lasting (36+ months) tumor response. Global geneomic sequencing revealed biallelic inactivation of the gene encoding PalB2 protein in this patient's cancer, the mutation is predicted to disrupt BRCA1 and BRCA2 interactions critical to DNA double strand break repair. This work suggests that inactivation of the PALB2 gene is a determinant of response to DNA damage in pancreatic cancer and a new target for personalizing cancer treatment. Integrating personalized xenografts with unbiased exomic sequencing led to customize therapy, tailored to the genetic environment of patient's tumor and identification of a new biomarker of drug response in a lethal cancer.