Gobbling up Poison: A Method for Killing Colon Cancer

The gist: This article describes a new cancer drug called MLN0264. The article focuses on its potential to treat colorectal cancer, but the drug is already being given to people with stomach cancer and prostate cancer in clinical trials—research studies with volunteer patients.

“These days, cancer researchers aim to design targeted and specific therapy – those that kill cancer but spare the surrounding tissue. Immunotoxins, which use cancer-targeted antibodies linked to deadly toxins such as ricin, are one such therapy. However, few have succeeded to date in part because cancer cells share many molecules with normal cells, and because it can be challenging to unlock the deadly chemical only after the antibody has homed to the diseased tissue.

“Now researchers at Thomas Jefferson University have discovered the unique biological properties inherent to colon cancer that make it a perfect candidate for immunotoxins – an antibody that won’t attach to normal cells and a toxin-delivery system that takes advantage of a fluke of biology: Colon will gobble up poison if it’s attached to a key receptor on the cell’s surface. Indeed, the researchers demonstrated that the novel immunotoxin they created could reduce the lung metastasis in mice, which had grown out from colon cancers, by more than 80 percent with only 6 doses, in research published September 8th, 2014 in the journal Oncotarget.

” ‘These studies pave the way for effective antibody-directed therapy for in , which currently carries a greater than 90 percent chance of mortality’ says Scott Waldman, M.D., Ph.D., Chair of the Department of Pharmacology Experimental Therapeutics and the Samuel MV Hamilton Professor at Thomas Jefferson University.”


Botox for Stomach Cancer? No, But the Research is Fascinating

Editor’s note: This article clarifies misleading claims made by other sources that Botox can now be used to treat cancer. However, the claims are based on research that is still very interesting. Read the article to separate the fact from the fiction. 

“Amid continuing tales of global woe, Thursday morning’s news carried one of those quirky ‘fancy-that!’ medical research stories that often captures the imagination, but which can inadvertently raise false hope in patients.

“According to several news outlets, Botox injections – better known for their face-freezing properties – ‘could be used to treat stomach cancer’. The Irish Independent’s headline even went so far as to say it was a ‘highly effective’ treatment.

“As is so often the case, that’s going way beyond what the underlying research actually found: the study was mainly carried out in mice, and doesn’t yet prove that Botox could help stomach cancer patients.

“But with that important caveat out of the way, the research itself is worth a closer look. It highlights a very poorly studied but fascinating topic – the potential link between the body’s nervous system and the way cancer develops…

“As a result of their findings, the Norwegian researchers have started a very small-scale clinical trial, in very advanced stomach cancer patients, to begin to test the idea that injecting Botox into stomach tumours might be helpful.”


Stomach Cancers Separated into Four Distinct Types

Stomach cancer cells (via Wikimedia Commons)

“US researchers have shown that stomach cancer is at least four separate diseases.

“The findings, published in the journal Nature, could rapidly lead to new clinical trials focusing on the different forms. Drugs are already available that target the genetic faults behind some of them.

“Experts from The Cancer Genome Atlas Research Network – a US-wide government-funded research project – analysed 295 samples of stomach cancers to find similarities that may be targeted when developing treatments.

“Research into the biology of stomach cancer and the development of new therapies has been difficult because of the different forms that the disease can take.

“Lead author Dr Adam Bass, from the Dana-Farber Cancer Institute, said that, despite stomach cancer being a diverse disease up until now researchers had tended to take a ‘one-size-fits-all’ approach to stomach cancer treatments.”

Editor’s note: For other cancer types, including lung cancer and melanoma, doctors often prescribe drugs that are personalized according to mutations found in patients’ tumors. Learn more about personalized cancer treatment.

Image: Stomach cancer cells (via Wikimedia Commons)


Adjuvant Radiation Therapy Improved Survival in Diffuse-Type Gastric Cancer

Editor’s note: Researchers conducted a clinical trial with volunteer patients to test whether giving radiation after tumor-removal surgery could stave off recurrence for people with diffuse-type gastric cancer. A treatment that follows an initial treatment to reduce the risk of the cancer returning is known as an “adjuvant therapy.” In this clinical trial, patients who received adjuvant radiation therapy after surgery survived significantly longer than patients who did not.

“Patients with diffuse-type gastric cancer demonstrated prolonged OS when they received adjuvant radiation therapy, according to results of a SEER analysis.

“Alexander M. Stessin, MD, PhD, of the department of radiation oncology at Weill Cornell Medical College, and colleagues used the 2002 to 2005 SEER database to identify 1,889 patients with newly diagnosed diffuse-type gastric cancer who underwent surgical resection. Of these patients, 782 received adjuvant radiation therapy and 1,107 did not.

“Patients who received adjuvant radiation therapy were younger, more likely to have ≥15 dissected lymph nodes and more likely to have N3 lymph node status. They also had a higher American Joint Committee on Cancer disease stage.”


Long Noncoding RNA in Gastric Juice, Plasma May be Marker for Gastric Cancer

The gist: Oncologists sometimes run tests to measure the amount of specific substances in a patient’s tumor(s) or other parts of his/her body that can help shed light on the details of the patient’s disease. These substances are known as biomarkers. Researchers recently discovered that a biomarker called “long noncoding RNA-AA174084” (also known simply as AA) could be used to help understand the severity of a patient’s gastric cancer diagnosis. Different levels of AA in tumors, gastric juice, and blood plasma were associated with disease characteristics like lymph node spread, benign tumors, tumor spread, and more.

“Changes in long noncoding RNA-AA174084 levels in the tissues, gastric juice and plasma of patients with gastric cancer were associated with clinicopathological factors, suggesting utility as a biomarker for early screening and predicting prognosis, according to research data.

“To determine the diagnostic and prognostic utility of plasma and gastric juice levels of AA174084 (AA) — a long noncoding RNA (lncRNA) found with abnormal expression in gastric cancer (GC) tissues in a previous study — researchers analyzed samples from three gastroenterology centers in China from February 2011 to November 2013. Total RNA was extracted from 860 patients and controls and measured using real-time reverse transcriptase-polymerase chain reaction analysis.

“AA levels were down-regulated in 71% of 134 GC tissue samples compared with paired adjacent normal tissues (P.001), with mean expression level 3.18 times greater in the normal samples. AA levels also were decreased in the GC samples and in 28 gastric dysplasia (GD) samples compared with 37 healthy gastric mucosa samples (P.01 and P.001, respectively). AA tissue levels negatively correlated with age (P=.031), Bormann type (P=.016) and perineural invasion (P=.032).”

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Basilea Announces Start of Phase 2a Study with Oncology Drug Candidate BAL101553

“Basilea Pharmaceutica Ltd. (SIX: BSLN) reports today that it initiated a phase 2a study with its investigational oncology drug BAL101553. The study is designed to further characterize safety and tolerability, and to obtain efficacy data in adult patients with advanced or recurrent solid tumors who have failed standard therapy or for whom no effective standard therapy is available. Tumor types were selected based on clinical observations in the phase 1 study and a detailed analysis of potential patient stratification biomarkers across tumor indications. The study will also continue the extensive biomarker testing initiated in Phase 1, to further evaluate dose and patient populations most likely to respond.”

Editor’s note: A drug company is starting a clinical trial to test a new cancer drug called BAL101553 in volunteer patients. The trial is enrolling people with advanced or recurrent solid tumors, including people with colorectal cancer, gastric cancer or cancers of the gastro-esophageal junction, non-small cell lung cancer (NSCLC), ovarian cancer (or primary peritoneal), pancreatic cancer (including ampullary), and triple-negative breast cancer. Specifically, the trial is open to patients who have tried a standard treatment without benefitting or who, for whatever reason, have no effective standard treatment available to them. BAL101553 has already shown promise for some patients in a phase I trial. The new trial will continue to examine the safety and effectiveness of the drug, and it will also test patients’ tumors for specific biomarker molecules to see if patients with certain biomarkers are more likely to benefit.


PD-1 Blocker Extends Life in People with Melanoma in Early Trial

An experimental immunotherapy may keep people with melanoma alive for up to 1 year, according to findings presented at the 2013 International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. The drug (MK-3475) blocks a protein, called PD-1, that lets cancer cells evade the immune system. Researchers treated 135 people with MK-3475 and found that tumors shrank in 40% and disappeared in 9%. Altogether, this drug is being tested in more than 3,000 people with melanoma or breast, bladder, colorectal, or lung cancer. In addition, another experimental PD-1 blocker called nivolumab is being tested alone and in combination with the U.S. Food and Drug Administration (FDA)-approved Yervoy (ipilimumab) against melanoma and blood, breast, gastric, kidney, liver, lung, and pancreatic cancers.


Experimental PD-1 Blocker May Work Across Cancer Types

Results of a phase I clinical trial suggest that a new immunotherapy drug called MPDL3280A could control a wide range of cancers. Manufactured by Roche Genentech, MPDL3280A is one of several promising but experimental drugs that block PD-1, a cell surface protein that disguises tumor cells from our immune systems. The study included 140 people with different kinds of tumors (melanoma as well as colorectal, gastric, kidney, and non-small cell lung cancers) that had resisted other treatments. Tumors shrank in 21% of those treated with MPDL3280A, particularly people with melanoma or lung cancer. These findings were presented at the 2013 meeting of the American Society of Clinical Oncology. While still in the very early stages of research, targeting tumors with our own immune systems has great potential to work across many different cancer types and to keep them in check longer than current treatments, say researchers, giving new hope to people with cancer.


Experimental PD-1 Blocker May Work Across Cancer Types

Results of a phase I clinical trial suggest that a new immunotherapy drug called MPDL3280A could control a wide range of cancers. Manufactured by Roche Genentech, MPDL3280A is one of several promising but experimental drugs that block PD-1, a cell surface protein that disguises tumor cells from our immune systems. The study included 140 people with different kinds of tumors (melanoma as well as colorectal, gastric, kidney, and non-small cell lung cancers) that had resisted other treatments. Tumors shrank in 21% of those treated with MPDL3280A, particularly people with melanoma or lung cancer. These findings were presented at the 2013 meeting of the American Society of Clinical Oncology. While still in the very early stages of research, targeting tumors with our own immune systems has great potential to work across many different cancer types and to keep them in check longer than current treatments, say researchers, giving new hope to people with cancer.