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.

Cancer Drugs Losing Out: Pruning the Branches, Not Cutting the Trees

An oncologist puts the cancer patient on a targeted therapy, the cancer goes away, patient goes home. But, 6 months later, the cancer is back (relapsed) and is aggressive stage IV. Biologically, the cancer cells have mutated to bypass/ignore the expensive targeted therapy.

At the molecular level, the cancer cells are constantly mutating, evolving, and generating diversity. This phenomenon of cancer evolution is central to cancer relapse, tumor escape and therapeutic failure.

New research from the Institute of Cancer Research, UK, shows extreme diversity of cancer cell types in leukemia patients: multiple cancers within a cancer. 

Taking the bite out of second cancer risk attributable to radiotherapy of primary first cancer

 Extract of my guest post at maiBlog, a radiology-focused blog.

"The increasing ranks of cancer survivors have brought new concerns into focus—second primary cancers now account for 18% of all cancer diagnosis and are the third most common cancer diagnosis in US. ... Radiotherapy, while a highly effective cancer treatment option, has long been considered to increase the risk of subsequent cancers, but convincing data had been lacking.  Now, an epidemiological study published by the National Cancer Institute in the April 2011 issue of Lancet Oncology journal shows that 92% of all second cancers are due to causes other than the radiation treatment of previous cancer. ..."

Click here to read full post at maiBlog.

(Find complete post at InternetArchive here.) ___________________________

Complete Post Below:

By Ajay K Malik, PhD

Over the last forty years, we have made great strides in the diagnosis and treatment of cancer. According to the Centre for Disease Control and Prevention (CDC), the number of cancer survivors have steadily increased from three million in 1971 to over eleven million today; one in twenty Americans is a cancer survivor. The increasing ranks of cancer survivors have brought new concerns into focus‚Äîsecond primary cancers now account for 18% of all cancer diagnosis and are the third most common cancer diagnosis in US. Similar data is also emerging from other countries. Second primary cancers (a.k.a. second cancers) are new cancers that arise after the first incidence of any cancer. Second cancer may be in the same, surrounding or distant organs, and differ from metastatic cancer which is a result of primary first cancer cells disseminating to a distant organs (see a definition here).

Genetics and lifestyle behaviors, for instance, smoking, alcohol or poor diet, are partly responsible for second cancer, the treatment modalities during first cancer may also have a role. Both chemotherapy and radiotherapy can increase predisposition of other cells to cancer. Radiotherapy, while a highly effective cancer treatment option, has long been considered to increase the risk of subsequent cancers, but convincing data had been lacking. Now, an epidemiological study published by the National Cancer Institute in the April 2011 issue of Lancet Oncology journal shows that 92% of all second cancers are due to causes other than the radiation treatment of previous cancer.

This study relied on a National Cancer Institute resource called US Surveillance, Epidemiology and End Results (SEER) cancer registries. Since 1973, SEER registries have been collecting and reporting data on patient demographics, cancer diagnosis, tumor morphology tumor stage at diagnosis, first-line treatment and follow-up status. There are fifteen SEER registries which cover 28% of the US population from Conn. to Calif. with a racial make-up reflecting the overall US population. The authors analyzed data (collected from nine registries) for 647,672 patients who were 20 years or older (adult) and had been followed for a mean of 12 years since the primary cancer diagnosis. Their analyses included all (i.e., fifteen) solid-cancer sites, and cancers which had appeared after 5 years of first cancer were counted as second cancers. In this analysis, patients who had survived five or more years, nine percent developed second tumors‚Äînot all had received radiotherapy.

Radiotherapy, as part of initial first cancer management included external beam, brachytherapy or a combination of both. There was a variation in the use of radiotherapy across various cancer types. In this cohort, 60-80% of testicular (seminomas), brain, anal and laryngeal cancers were treated with radiotherapy, whereas less than 30% of non-small-cell lung and eye & orbit cancers were managed with radiotherapy. Yet, for every cancer type analyzed, the risk of second cancer was significant (Relative Risk, RR>1); the highest risk was for testicular (34%) and cervical(17%) cancers. However, of all the second cancers, only 8% could be attributed to radiotherapy during first cancer management. This is a much smaller percent than expected, and is a very good news for the radiology community. It helps communicate long-term risk of radiotherapy with respect to the potential benefit of tumor control and patient survival. Furthermore, the overall risk also decreases with time and by 15 years after the first diagnosis, only five excess cancers were found per 1000 cancer survivors.

The strengths of this study were: systemic analysis of all first cancer sites in adults, large population and over three decades of follow-up population data. However, there are some limitations: pediatric populations were excluded, also excluded from the study were patients who survived <5 years, those with hematological cancers, non-seminoma testicular cancers and small-cell lung cancer. The radiotherapy tools and equipment are continuously evolving and new technologies are being adopted. Thus, another look at these statistics will be warranted in coming years. But, for now, radiotherapy must be considered safe and should help professionals address anxiety of patients choosing a radiotherapy option.

This study was led by Amy Berrington de Gonzalez of Radiation Epidemiology Branch of National Cancer Institute, Bethesda, and included researchers from MD Anderson Cancer Institute, Houston, Texas.

Read more about the author, cancer biologist and biotech writer,Ajay K. Malik, PhD

References

Cancer Survivors‚ÄîUnited States, 2007. Morbidity and Mortality Weekly Report (MMWR). March 11, 2011;60(9):269-272 | FreeFullText |

de Gonzalez AB, Curtis RE, Kry SF, et al. Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries.Lancet Oncol. 2011 Apr;12(4):353-60. | PubMed | Scholar |

Tags: radiation therapy, radiotherapy, secondary cancer

Friday Grand Rounds: Harold Varmus Discusses Cancer Cell Biology and Clinical Translation

Thirty-five years ago Harold E. Varmus [wikipedia], along with J. Michael Bishop, discovered the role of oncogenes in cancer.  That seminal discovery in 1975 gave cancer researchers a path, "the road to be taken," that has today led to great advancements in clinical oncology; it has changed the face of a growing number of cancer types to potentially curable or manageable forms.  Not long ago, both scientists were honored with the Nobel Prize in Medicine in 1989 [read, [here, here]

Verastem brings CSC target into “sharper” focus

The launch of Verastem, Inc., in Boston last week with the securing of $16 million Series A financing , signals the coming of age of cancer stem cells (CSCs) as a target for solid cancers. 

Cancer is (NOT) a modern, man-made disease

Last week, what started as a press release by the University of Manchester to publicize an opinion article by its faculty, and picked up by some ‘reputable' media (like Telegraph), led to a tsunami of rebuttals and jabs all over the blogosphere.