Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer

The point of this article focused on the impact of long-term aspirin and the risk of cancer. The study stemmed from the recommendation of the US Preventive Services Task Force that aspirin can be used to help prevent colorectal cancer and cardiovascular disease. The study wanted to address the effectiveness of aspirin in other cancers. In the study they took two large US prospective cohort studies that had over 135,000 participants. The studies were long term and done over many years and accessed medical records to evaluate a patient’s different types of cancers. The study was completed over 32 years. By the end of the study it was found that aspirin can reduce the overall risk, especially in GI cancers.

I think this study was important since aspirin is such a widely utilized and recommended medication by doctors and pharmacists. Aspirin is primarily recommended for heart protection and health, but now shows an even added benefit of cancer prevention. As pharmacists this gives another important tool for showing patients the benefit of taking aspirin on a regular basis. While I think this is an important indication, I do no think there is enough evidence to support aspirin therapy simply for cancer prevention. More research should be done to continue to weigh the pros and cons of aspirin therapy for the prevention of cancer.

 

Cao Y, Nishihara R, Wu K, et al. Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer. JAMA Oncol. Published online March 03, 2016. doi:10.1001/jamaoncol.2015.6396.

http://oncology.jamanetwork.com.pitt.idm.oclc.org/article.aspx?articleid=2497878

Combination therapy may be better than radiotherapy alone to treat aggressive brain cancer

It is known that radiotherapy is effective in damaging brain tumors, but radiotherapy does not fully kill the tumor because the cancer cells can repair themselves and keep living.  Researchers at Sidney Kimmel Cancer Center are now testing a combination of radiotherapy and a drug called panobinostat that makes the cancer cells unable to repair themselves. The researchers are testing the combination on aggressive, recurrent brain cancer.  They feel that panobinostat makes radiotherapy much more effective.

Currently, there is no standard treatment for gliomas other than radiation.  Most patients will not live very long.  The efficacy of panobinostat is hopeful for improving survival rates.

Panobinostat was approved for use in 2015 for treatment of multiple myeloma, and now it is being tested to treat other cancers. It is a histone deacetylase inhibitor; it works by modifying RNA to change protein production and turns off RAD51 (a DNA repair enzyme) which upsets cancer growth.

Researchers found that the highest doses of panobinostat were well tolerated and improved survival.  Overall, researchers found that this cancer drug was very safe and that there is promise to treat other drugs.

The question I will pose is:  If the drug works by changing protein production and turning off DNA repair enzymes, wouldn’t you think it would cause bad side effects?  Yet it was shown to be very safe at even the highest doses.

 

 

Wenyin Shi, Joshua D. Palmer, Maria Werner-Wasik, David W. Andrews, James J. Evans, Jon Glass, Lyndon Kim, Voichita Bar-Ad, Kevin Judy, Christopher Farrell, Nicole Simone, Haisong Liu, Adam P. Dicker, Yaacov R. Lawrence.Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas. Journal of Neuro-Oncology, 2016; DOI:10.1007/s11060-016-2059-3

Risks of using herbal medicines in cancer patients

A study published in the journal of Cancer found that herbal remedies and supplements such as turmeric can increase the toxic effects of certain chemotherapies. Similarly, they found that green teas and gingko biloba can increase the risk of bleeding in these cancer patients.

The study was focused on cancer patients in the Middle East since herbs are commonly used as traditional medicine. The study found that nearly two-thirds of the herbal medicines that cancer patients in the Middle East used pose potential health risks.

I think this study is very important because a lot of people tend to think that anything that is over-the-counter or natural is safe. This is why it is important for patients to inform all of their healthcare providers about all of the over-the-counter medicines and supplements they take. My questions for the class are: What do you think of herbal medicines and how safe do you think they are for the average person?

Reference:

Eran Ben-Arye, Noah Samuels, Lee Hilary Goldstein, Kamer Mutafoglu, Suha Omran, Elad Schiff, Haris Charalambous, Tahani Dweikat, Ibtisam Ghrayeb, Gil Bar-Sela, Ibrahim Turker, Azza Hassan, Esmat Hassan, Bashar Saad, Omar Nimri, Rejin Kebudi, Michael Silbermann. Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals. Cancer, 2016; 122 (4): 598 DOI:10.1002/cncr.29796

DNA ‘Trojan horse’ smuggles drugs into resistant cancer cells – Cells mistake DNA casing for food, consume drugs and die

Researchers at Ohio State University are working on a new method to treat resistant cancer cells.  Since the cancer cells are resistant, they are no longer affected by the cancer drugs the patient has been taking.  However, when researchers encapsulated one of the resistant drugs in DNA, the resistant cells mistook the drug for food, ate it, and died.  This technique is called “DNA Origami” and it has only been used to treat solid tumors, never before used to treat drug-resistant leukemia cells.

The researchers have been testing this method in mice, and hope to move onto humans within a few years.  The researchers are studying acute myeloid leukemia (AML) that is resistant against the drug daunorubicin.  When daunorubicin enters an AML cell, the cell recognizes them and pumps them back out through openings in the cell wall, much like a sump pump.

The new method they are exploring hiding is like a “trojan horse” becuase daunorubicin is hid inside a DNA shell that can bypass the pumps so they can’t eject the drug from the cell.  The drug accumulates and then causes the cell to die.

There is also hope to tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects.

DNA origami nanostructures have great potential for drug delivery.  The drug the researchers were studying in this research worked by going into the cancer cell’s DNA and preventing it from replicating.

 

The question I will ask is:  Knowing that DNA origami has been used to treat solid tumors but never before leukemia, do you think this cancer treatment method will work in other types of cancers? Why or why not?

 

 

 

Patrick D. Halley, Christopher R. Lucas, Emily M. McWilliams, Matthew J. Webber, Randy A. Patton, Comert. Kural, David M. Lucas, John C. Byrd, Carlos E. Castro. DNA Origami: Daunorubicin-Loaded DNA Origami Nanostructures Circumvent Drug-Resistance Mechanisms in a Leukemia Model (Small 3/2016). Small, 2016; 12 (3): 307 DOI:10.1002/smll.201670014

Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition

For years now, COX-2 inhibitors have been used to treat pain and inflammation. Recently, much research has suggested that they may potentially be able to reduce tumour processes. COX-2 can be upregulated by tumor promotors, revealing that it may be involved in pathological processes of various types of cancer. Currently, there are hundreds of clinical trials being conduced testing the anti-tumor properties of COX-2 inhibitors such as celecoxib.

The investigators in this study created new COX-2 inhibitors derived from an analysis of currently known COX-2 inhibitors. One of the dihydropyrazole sulphonamide derivatives developed, 4d, demonstrated high COX-2 selectivity and anticancer properties. Further, it was shown that 4d could stop the cell cycle at the G2/M phase. It also induced apoptosis in A549 (tumor cell-line) cells. Overall, it seems that compound 4d could potentially be utilized for cancer treatment.

Qiu H, Wang P, Zhen L, et al. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. Pharmacol Res. 2016;104:86-96.

 

New Cancer Drug Vermurfenib Treats BRAF V600 Mutation in Both Melanoma and Nonmelanoma

The BRAF V600 mutation occurs in almost 50% of melanomas and results in activation of a MAPK pathway. Vemurafenib, a new cancer, is an inhibitor of the BRAF V600 kinase and is associated with a 50% response rate and improved survival in patients with the BRAF V600 mutation who also have metastatic melanoma. The efficacy of vermurafenib in nonmelanoma cancers has not been heavily studied. Thus to treat nonmelanoma cancer patients with the BRAF V600 gene, Hyman and his colleagues designed a study to test the efficacy of vermurafenib in other various types of cancer.

 

The study included patients with the following nonmelanoma cancers: non-small-cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, and breast cancer. The primary outcomes was to measure the response rate of the drug, progression of the tumor, and overall survival rate. In the group with the non-small-cell lung cancer, the response rate was 42% and the survival rate extended 7.3 months. There were positive responses in the drug treating the other variations of cancer, but this was the most significant one. Therefore the BRAF V600 gene is a good target gene for some nonmelanoma cancers, especially non-small-cell lung cancer. In addition, vemurafenib is a drug that can treat both melanoma and nonmelanoma cancer.

 

It is always encouraging when a new cancer drug is developed and proven to be effective. What is so remarkable about this drug is that although it treats a very specific gene mutation, it treats a significant amount of different outcomes from this mutation. Non-small cell lung cancer is a type of lung cancer that causes death in 50% of its patients so finding a drug that can prolong life and decrease tumor growth is a great accomplishment.

 

Hyman D, Puzannov I, Subbiah V, et al. Vermurfenib in multiple nonmelanoma cancers with BRAFV600 Mutations. N Engl J Med. 2015; 373:726-736.

 

 

High sucrose diet linked to increased risk in breast cancer

Researchers at The University of Texas MD Anderson Cancer Center have been studying how dietary sugar effects enzymatic signaling of the 12-LOX (12-lipooxygenase) pathway. The researchers found that mice who had sucrose intake similar to those found in Western diets lead to an increased risk of tumor development and metastasis. Specifically, they studied the impact of how sucrose influenced mammary gland tumor development in several mouse models.

This is the first study to investigate the direct effect of sugar consumption and how it relates to the development of breast cancer. The researchers believe that the mechanism by which the sugar effects tumor growth, the 12-LOX pathway, needs to be further studied.

I think this article is very interesting because I had never even thought of dietary sugar levels leading to cancer development. This is important as a pharmacist because we can make recommendations to patients to eat healthier or refer them to a dietician. If this data holds true in humans, it will be another great counseling point to make in order for our patients to eat less unnecessary sugar to improve overall health. My questions for the class are: Have you ever thought that excess dietary sugar could lead to cancer development? And, if the data translated to humans, do you think people would change their diet if they knew this information?

 

Reference:

Yan Jiang, Yong Pan, Patrea R. Rhea, Lin Tan, Mihai Gagea, Lorenzo Cohen, Susan M. Fischer, and Peiying Yang. A Sucrose-Enriched Diet Promotes Tumorigenesis in Mammary Gland in Part through the 12-Lipoxygenase PathwayCancer Res, January 1, 2016 76:24-29 DOI: 10.1158/0008-5472.CAN-14-3432

Appalachia continues to have higher cancer rates than the rest of US, but gap is narrowing

Appalachia, a region of the US that contains Pittsburgh (Appalachia stretches from New York to Mississippi and contains 25 million people), has higher cancer rates than the rest of the nation; contributing factors are higher tobacco use, lower socioeconomic status, and patient health care utilization.

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a study that showed higher cancer rates in Appalachia between 2001 and 2003; however, the study had some shortcomings.  A more thorough study was done between 2004 and 2011, and it contained data from both Appalachian populations and non-Appalachian populations.  This study was able to analyze 100% of the US population by using data from the National Program of Cancer Registries (NPCR) and data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.

The data from the Appalachian population was divided into three groups:

  • residents from three regions (counties in the north, central, and south Appalachia)
  • by gender, race (black and white)
  • by Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment

This was then compared with data on the non-Appalachian population, and the results showed that “the cancer incidence rates were elevated among Appalachians regardless of how they were categorized.”

Even though Appalachia has a higher incidence of cancer as compared to the rest of the country, the gap is narrowing (with the exceptions of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid).  It is promising to note that the gap between Appalachia and non-Appalachia has narrowed since 2007.

This study is important because it shows the importance of screening for cancers and diseases for at-risk populations.  It also shows the importance of lifestyle.  For example, not using tobacco products will make you less at risk for cancer.  And if you do use tobacco products, it is important to be screened for cancers more regularly since you are more at risk.

The question I will pose is:  What initiatives can we take to decrease the rate of cancer in Appalachia?

 

Reda J. Wilson, A. Blythe Ryerson, Simple D. Singh, and Jessica B. King.Cancer Incidence in Appalachia, 2004–2011. Cancer Epidemiol Biomarkers Prev, February 2016 DOI: 10.1158/1055-9965.EPI-15-094

PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses

The programmed cell death protein 1 (PD-1) checkpoint is a step in a pathway that prevents the activation of T-cells. Inhibitors of this pathway are designed in order to restore a patient’s antitumor immune response, which becomes suppressed during formation of tumors. Once the T-cells are activated, the immune system starts to attack tumors in the body. Immuno-oncology agents that can restore antitumor immune responses are a new class of medications that have just recently been approved for clinical use. Medications nivolumab and pembrolizumab are two such immuno-oncology agents used to inhibit the PD-1 pathway.

Researchers in this article highlight the response characteristics distinctive to immune checkpoint inhibitors as well as provide pharmacokinetic and pharmacodynamic data for pharmacists and physicians. These researchers have studied these new medications in those with advanced melanoma, metastatic non-small cell lung cancer, and advanced renal cell carcinoma. But although there are many benefits to using these drugs, there have also been many adverse events encountered in those taking this new class of medication. Along with the classic immune-mediated adverse effects expected to be seen when taking anti-cancer drugs, the PD-1 inhibitors also have potential for developing autoreactive T-cells, leading to inflammation across a range of tissues. It is for this reason that patients with a history of autoimmune diseases were excluded from these clinical trials. Despite these adverse reactions, survival rates of the patients taking these medications have increased compared to patients taking standard treatment options.

I feel that although there are many adverse events associated with this new class of cancer drug, and although these drugs were hastened to become approved by the FDA, their efficacy is greatly needed in the management of various cancers. And as demonstrated in the article, if pharmacists collaborate with physicians effectively, the majority of immune-mediated adverse effects can be managed with concurrent use of other medications to ease these symptoms without discontinuation becoming necessary.

Medina, Patrick J., and Val R. Adams. “PD-1 Pathway Inhibitors: Immuno-Oncology Agents for Restoring Antitumor Immune Responses.” Pharmacother. (2016): n. pag. Wiley Online Database. Web. 15 Feb. 2016.

http://onlinelibrary.wiley.com/doi/10.1002/phar.1714/abstract

BRCA Mutation Testing in Young Women With Breast Cancer

In young women diagnosed with breast cancer, BRCA testing is recommended. This study looked at the decisions surrounding testing and how results may influence treatment decisions. The study’s objective was to describe the genetic testing and evaluate how concerns about genetic risk affect treatment decisions in these young women. There were 897 women aged 40 years and younger observed that all had a breast cancer diagnosis.

A total of 780 women (87%) reported BRCA testing by 1 year after breast cancer diagnosis. This study took place from the year 2006 to the year 2014. As the years went on, a bigger percentage of women reported testing. For example, in 2006, 30 of 39 women (76.9%) reported testing. In 2008, 141 of 146 women (96.6%) tested. Among the untested women, 43 of 117 (36.8%) were thinking of testing in the future. A total of 248 of 831 women (29.8%) said that knowledge or concern about genetic risk influenced surgical treatment decisions. In conclusion, rates of BRCA mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influences surgical decisions, all women with breast cancer should be counseled and offered genetic testing.

We have started talking a good amount about the genetic role in pharmacy and pharmacotherapy. Do you think that genetic testing, especially in cancer, should be pushed for more? Does this testing actually benefit patients or just get them worried and thinking more? I think genetic testing is a great tool for health professionals to have and we should use it to our advantage as much as possible. The problem is, however, getting the public on board with it. What is the best way to accomplish that?

JAMA Oncol. Published online February 11, 2016. doi:10.1001/jamaoncol.2015.5941