3 Primary Ways Researchers Are Combatting Cancer

In In The News by Barbara Jacoby

By: Sean Williams

From: madison.com

Among the countless ailments a person can be diagnosed with, cancer is arguably the scariest. Worse yet, the odds of developing cancer are probably higher than many realize. Data from the U.S. National Cancer Institute’s Surveillance Epidemiology and End Results database between 2010 and 2012 shows that men have about a 42% chance of developing cancer throughout their lifetime and 38% for women. Tack on estimates from the World Health Organization that cancer incidence rates could rise nearly 60% over the next decade, and you have a very good picture of why there’s such fear surrounding this disease.

Unique ways researchers are fighting cancer

Clinical researchers, however, aren’t standing idly by. Instead, billions of dollars are being invested annually by drugmakers and universities in an attempt to unlock the secrets of cancer, with the ultimate hope of one day bringing cures to a disease that once had no solutions.

These “solutions” are primarily taking three shapes (although there are far more than three ways researchers are tackling cancer): monoclonal antibodies, checkpoint inhibitors, and cancer vaccines. Let’s take a brief look at how each is combatting cancer.

1. Monoclonal antibodies

Antibodies are proteins that circulate throughout our bodies seeking an antigen, or foreign substance that elicits an immune response. Once the antibody has found the specific antigen it’s seeking, it attaches, attracting the attention of the immune system, which will then destroy the cell. Unfortunately, cancer cells often have immunosuppressant qualities that allow them to avoid immune detection. Thus, researchers have been hard at work in the lab creating copies of antibodies that target very specific antigens that are believed to be important in cancer growth. These man-made, cancer-seeking antibodies are known as monoclonal antibodies.

There are a number of exciting monoclonal antibodies already on pharmacy shelves, many of which refine the fight against cancer.

Perhaps the best-known monoclonal antibody is Roche‘s (NASDAQOTH: RHHBY) Herceptin, which is used to treat breast cancer and gastric cancer patients whose tumors express HER2 (known as HER2+). When this protein is found on the outside of cancer cells and is activated, it can spur cancer growth. Herceptin works to inhibit the interaction of the HER2 protein by binding to it, thus stopping the interaction that leads to cancer growth. Herceptin has been around for well over a decade now, and it’s probably no surprise that this effective inhibitor of HER2 brought in $6.6 billion in sales in 2015, a 10% jump from the previous year.

An equally exciting type of monoclonal antibody that potentially offers cancer-killing potential are conjugated monoclonal antibodies such as antibody-drug conjugates. Antibody-drug conjugates, or ADCs, use antibodies that seek out a specific antigen, but they also have a linked toxin (i.e., chemotherapy) that releases once the antibody binds with the antigen. The idea is that the ADC will directly target cancer cells with a specific protein signature, thus causing the release of the chemotherapy and sparing healthy cells from death, as would be seen in a global chemotherapy treatment.

One of the most exciting ADCs already on the market is Seattle Genetics(NASDAQ: SGEN) Adcetris, which is designed to target the CD30 antigen that’s found on lymphocytes (white blood cells). Adcetris is approved to treat Hodgkin lymphoma, as well as anaplastic large cell lymphoma. Seattle Genetics believes Adcetris could have more than $1 billion potential given its effectiveness at targeting CD30 in clinical trials, and the fact that there are nine ongoing mid- or late-stage studies examining Adcetris in frontline or relapsed blood cancer indications. The company also has more than 15 ongoing collaborations, signaling the desire for drugmakers to defeat this disease.

2. Checkpoint inhibitors (a.k.a. cancer immunotherapies)

Without question, cancer immunotherapies have to be the most exciting form of cancer drug research at the moment. Immunotherapies aim to tackle the immunosuppressant quality of cancer by exposing cancer cells to the wrath of the immune system, while also supercharging the immune system to attack. The most prominent form of immunotherapies are checkpoint inhibitors.

Currently, there are three approved checkpoint inhibitors on pharmacy shelves. These include Bristol-Myers Squibb‘s (NYSE: BMY) Opdivo, Merck‘s (NYSE: MRK) Keytruda, and Roche’s Tecentriq, the latter of which was the most recently approved.

The best known of the bunch are Opdivo and Keytruda, which are drugs targeted at programmed death-1, or PD-1. PD-1 is a checkpoint protein that’s found on T-cells, which is a type of immune system cell. PD-1 typically binds with PD-L1, or programmed death-ligand 1, which acts as an “off” switch to tell the immune system not to attack a select cell (which is a great thing for normal cells). However, cancer cells with a lot of PD-L1 receptors can avoid detection by having PD-1 bind to these receptors. Keytruda and Opdivo aim to shut down this interaction by inhibiting PD-1, thus removing cancer’s ability to hide from the immune system.

The early clinical results from both drugs has been incredible, and it’s been a testament to the true potential of these checkpoint inhibitor. Some studies, especially those with high PD-L1-expressing tumors, have demonstrated response rates as high as 60%. Bristol-Myers’ Opdivo is already approved to treat metastatic melanoma, second-line metastatic non-small cell lung cancer (NSCLC), and second-line metastatic renal cell carcinoma, whereas Merck’s Keytruda is approved to treat metastatic melanoma and second-line metastatic NSCLC patients whose tumors have high PD-L1 expression.

Both drugs are expected to be megablockbusters and could easily shape the future of cancer treatments via combination therapies.

3. Cancer vaccines

Lastly, researchers are combatting cancer through the use of cancer vaccines. Certain types of viruses, such as the human papillomavirus, can lead to cancer formation. For example, certain types of HPV have been associated with ovarian cancer development. Likewise, the hepatitis B virus can, over time, put an infected patient at a higher risk of developing liver cancer. Cancer vaccines can be targeted to either attack the virus that’s believed to cause cancer, or they can be geared to induce an immune response against cancer cells.

One of the best-known vaccines to make it to market is Valeant Pharmaceuticals(NYSE: VRX) Provenge, a vaccine designed to treat prostate cancer that Valeant acquired after Dendreon declared bankruptcy. Patients receiving Provenge would have some of their immune cells harvested by researchers who, in a lab, would expose these cells to a protein that would teach the immune system how to locate more prostate cancer cells in order to destroy them. These modified immune cells were then infused back into the patient. Although Provenge provided a greater than four-month survival benefit, its $93,000 price tag never quite caught on with patients or physicians. Valeant continues to offer Provenge, but traditional cancer treatment options remain the go-to in prostate cancer treatment.

An experimental cancer vaccine worth eyeing is Inovio Pharmaceuticals(NASDAQ: INO) VGX-3100, which is being targeted at cervical dysplasia caused by HPV types 16 and 18. VGX-3100 is currently in late-stage studies, but it delivered exciting results in a previously released midstage readout. In that readout, VGX-3100 reduced the grade of disease from CIN 2 or CIN 3 to CIN 1 or no disease in 49.5% of patients, and it led to the clearance of HPV and a regression from CIN 2/3 to CIN 1 or no disease in 40.2% of patients. By comparison, only 30.6% of placebo patients saw a regression in disease to CIN 1 or no disease, and just 14.3% also had HPV clearance.

There are a lot of exciting things going on with cancer research, and I personally look forward to seeing steady progress made in the fight against cancer.