Dogs Teaching Us a Thing or Two About Cancer Biology

The German shepherd standing on my front lawn, and his friends in the neighborhood, the rottweiler, the maltese, the shih tzus, the husky, and the other exotic breeds, have one thing in common: Like humans, they are living into their golden ages, and are increasingly showing up with diseases of old age, including cancer. Dogs once past the age of 10 years have a 50% chance of developing any type of cancer. (A 10 year old dog, depending on the breed, is same age as a 55-65 year old man.) 

All types of cancers seen in humans also show up in dogs. For example, take breast cancer: Like women, female dogs (those not neutered, or are at a breeder) also come down with breast cancer, generally called mammary cancer in dogs.

Further, not only the biology of cancer is similar in dogs and man, the dogs also respond to same cancer drugs that are used for humans.


Comparative Oncology

On March 31st, 2014, The New York Times profiled the Penn Vet Shelter Canine Mammary Tumor Program on its website. This innovative program, run by Dr Karin Sorenimo, the Professor of Oncology at the University of Pennsylvania, takes in shelter dogs for cancer treatment and care; the dogs in turn help advance research into the biology of cancer by ways that are impossible to do in humans.

Common Mutations Drive 12 Different Cancer Types

Cancer types from leukemia to breast cancer, and bladder cancer to lung cancer are all driven by a common set of genes containing driver mutations. Researchers from The Cancer Genome Network (TCGN) sequenced and analyzed genomes of 3,281 tumors from 12 different cancer types and discovered 127 genes that were involved in the initiation or progression of these cancers. This research appears in the October 17, 2013, issue of the journal Nature. 

Meeting Report: AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer

Lung cancer is the most common cause of cancer-related death, accounting for one-third of all cancer deaths.  Lung cancer is also the second most common cancer in men (after prostate cancer) and women (after breast cancer).  Over 200,000 people are diagnosed with and about 150,000 people die from lung cancer every year in the United States [a, b].  While surgery, chemotherapy and radiotherapy are routine treatment choices, in the recent years, patients have benefited from the introduction of targeted therapies based on the discovery of mutations in the EGFR and KRAS genes, and EML/ALK translocations.   EGFR mutations are more commonly found in non-small cell lung cancer (NSCLC) tumors in Asian population (30-40%) than Caucasians (10-15%).   About 4% of the patients carry EML/ALK translocation.


The ongoing 2012 AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer: Biology, Therapy and Personalized Medicine in San Diego highlights some of the recent advances in lung cancer biology, diagnosis and treatment (see below)

1000 Genomes, Clan Genomics and Cancer Biomarkers

The publication of human genome blueprint in 2000 was a great block party, summer Olympics coming to town, but the next morning saw most revelers picking up their drunken selves and going back to their old day jobs.  Some kept the flames burning by taking up more and more sequencing of whatever came their way labeled as a model organism.  The human genome blueprint was like a great idea which won a patent but still needed a lot of development work to morph into a cool product.

Post-human genome project

The launching of the 1000 Genomes Project in January 2008 was a true effort to translate the human genome blueprint into something that can really impact clinical practice and health care on a national scale.  The 1000 Genome Project was designed to sequence and catalog genetic variations from different ethnic groups across the globe.  The results of the pilot phase were published in Nature last year.

Shaping Cancer Diagnosis: Looking at the Horizon of Next Generation Sequencing and Targeted Resequencing

Two articles in this week's issue of Genetic Engineering & Biotechnology News reviewed recent trends in the next-generation sequencing and targeted resequencing technologies.  These advances are expected to further impact cancer diagnostics and treatment decision-making.

GNE Video: Understanding Biomarkers

Friday Grand Rounds are back, a day early because Jeff just flew in and can't wait to tell us all about Biomarkers. 

Webinar Report: Impact of Next Generation/Whole-Genome Sequencing on Companion Diagnostics

Biomarkers are increasingly part of pharmaceutical and clinical strategy.  By some estimates, the success rate of FDA approval of new cancer drugs is 75% if mechanism-of-action and predictive or prognostic biomarkers are clearly defined, whereas it is 25% without the biomarker information.  However, identifying new biomarkers for companion diagnosis (CDx) remains a challenge—the identification of KRAS-type biomarkers is rare, there is a double regulatory hurdle and revenue issues hamper pharmaceutical investment in this area.  Whole-genome sequencing is an important tool in the discovery of biomarkers. 

Striking the Heart of Hydra with miRNA

Cancer has long been depicted as a nasty crab.  Now Colin Barras describes it as a “distant animal ancestor, a ‘living fossil’ from over 600 million years ago.”  If cancer is an organism, it is an alien in our bodies.  An alien believed by many to be driven by cancer stem cells on an engine of endothelial-mesenchymal transformation (EMT) phenotype. 

Diagnostic Trailblazers in San Diego Advancing CDx, PGx and PM Goals in Cancer

Yesterday, I attended a half day symposium on companion diagnostics (CDx) efforts in San Diego which was organized by the SABPA Science & Technology Forum.  CDx is the identification and detection of biomarkers to predict whether a drug will work or not in a given patient.  Two successful marketed products are HercepTest (marketed by Dako) for Herceptin and KRAS tests for Erbitux and Vectibix.  San Diego biotech has a rich history and deep investments in diagnostics.  This was reflected in the lineup of various talks.

Helping Win Steve Jobs' Pancreatic Cancer Fight For All of US Because iPads Are Not the Only Things That Matter

Yesterday, Steve Jobs once again returned to the world stage to introduce Apple's new iPad2 and once again the spotlight was also put on his ongoing battle with pancreatic cancer. 

Friday Grand Rounds: Russ Altman Introduces Pharmacogenomics Database PharmGKB

Every human cell, with two sets of 23 chromosomes, contains six-billion basepairs of DNA (or three-billion per haploid genome).  Of these three-billion genomic basepairs, each individual shares 99.7% with the rest of the humanity.  It is the three-tenths of a percent that determines the differences between all of us.  This tiny percent, nevertheless, comprises of about a million positions that not only make us unique individuals, but also determine how we respond to environment, succumb to certain diseases, or respond (or not) to certain drugs.  These single nucleotide changes, scattered all over the genome, are called single-nucleotide polymorphism (SNP, pronounced snip) - for example, I may have Adenine at position X, you may have C and my friend may have G at the same position.  Since the complete sequencing of human genome in 2003, the post-genomic goal has been, to answer how this 0.3% of genome determines phenotype.  Pharmacogenomics/Pharmacogenetics (PGx) is the study of how genetic makeup correlates to responses to various drugs.  

Oncology Focused Pharmacogenomic "predictive" Biomarkers

Pharmacogenetics and pharmacogenomics (abbreviated together as PGx) are key to the future of personalized medicine.  Pharmacogenomic biomarkers provide tools to predict (a) drug response or (b) adverse drug reactions.  Such biomarkers help to maximize efficacy and minimize toxicity.