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.

Rethinking the scientific method: newyorker.com

Rethinking the scientific method: newyorker.com

The Truth Wears Off - Is there something wrong with the scientific method?

Is long-term solitary confinement torture?: newyorker.com

Is long-term solitary confinement torture?: newyorker.com

The United States holds tens of thousands of inmates in long-term solitary confinement. Is this torture?

by Atul Gawande

No survival benefit for Neoadjuvant Chemotherapy Compared With Surgery Alone for Locally Advanced Cancer of the Stomach and Cardia, results from EORTC trial 40954

Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. A Randomized EORTC trial (40954) examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. Authors found a significantly increased R0 (radical, no tumor left) resection rate in the preoperative chemotherapy group, but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including esophagogastric junction (AEG) and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study

Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients. These findings warrant further study of cetuximab plus GEMOX in a large randomised trial.

FOLFIRINOX: a new standard treatment for advanced pancreatic cancer?

by Richard Kim on Lancet oncology

Pancreatic cancer is still a lethal disease because of its tendency to undergo early subclinical metastasis to the regional lymph nodes and liver. Gemcitabine has been the standard chemotherapy for metastatic pancreatic cancer for many years on the basis of a phase 3 trial showing its clinical benefit over fluorouracil;1 however, the median survival was only 5·6 months and response rate only 5%. Since then, many trials have been done with gemcitabine being the backbone of the doublet or triplet regimens to improve overall outcome in patients.

Reconnecting with family

Research Overseas, a Nature Journal editorial

• Claire Thompson

This article was originally published in the journal Nature

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I left my native Australia nearly two years ago in a flurry of paperwork and last-minute packing. I tied up as many of the loose ends of my life as I could, put my finances in order and tried to work out what I could take with me without exceeding my baggage allowance. There seemed to be just enough time for tearful goodbyes at the airport before I was on my way to Germany.

This year, I returned to Sydney for a visit, courtesy of a conference that I was attending. It was an opportunity to present my postdoctoral work — and it was my first visit home.

Only a month before my trip, I had learned that my grandmother was ill. The high price of pursuing science overseas became all too clear: it is difficult to help and look after your family when you're half a world away. Worried, I had considered booking a flight to Sydney immediately, and pushing my trip forward by a month. The decision was not easy; there is no such thing as a quick dash home when the journey involves a 22-hour flight. If I had left then, half-done experiments would have gone to waste and my colleagues and students would have been inconvenienced, because I was in the middle of teaching a course. But after a few desperate calls to my parents, I learned that all was well — my grandmother was recovering.

I was extremely glad to see all my family when I landed in Sydney for the conference. My grandmother seemed to be in much better health. But the experience made me realize: although working overseas has many career benefits and has been a fantastic experience, the distance has significant drawbacks. I must try to put my experiments aside and take that 22-hour plane ride more often.