Molecular picture of how antiviral drug molnupiravir works

A cryo-EM structure showing how the antiviral drug molnupiravir drug Read more

Straight to the heart: direct reprogramming creates cardiac “tissue” in mice

New avenues for a quest many cardiologists have pursued: repairing the damaged heart like patching a Read more

The future of your face is plastic

An industrial plastic stabilizer becomes a skin Read more

targeted therapy

Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype.

Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients.

Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple myeloma cells with one type of chromosomal DNA rearrangement tend to be sensitive to venetoclax. About 20 percent of multiple myelomas carry this rearrangement, called t(11;14).

“One of our main goals is to identify a better biomarker to predict patient response to venetoclax,” says Winship researcher Vikas Gupta, lead author of a paper published in Blood earlier this year.

Vikas Gupta, MD, PhD

Gupta works together with Winship hematologist Jonathan Kaufman and researcher Larry Boise, also associate director for education and training, to translate insights about myeloma cells into advances for patient care.

In a recent clinical trial led by Kaufman, a sizable fraction of people whose myelomas carried the t(11;14) rearrangement responded well to venetoclax, when their cancers were already refractory to other drugs. Another study that did not separate out myelomas with t(11;14) extended progression-free survival by almost a year.

However, venetoclax also was associated with increased mortality from infections, which led the FDA in 2019 to put the second study on hold temporarily. Other ongoing studies of venetoclax with multiple myeloma were affected.  It highlights the need to predict which patients would benefit from venetoclax – and which would not be likely to, for whom the drug may pose more risk.

In their paper, Winship investigators discovered that a set of cell markers predicted sensitivity to venetoclax better than t(11;14). These were markers for B cells, a type of white blood cell related to both multiple myeloma and some of the other forms of leukemia and lymphoma venetoclax is used to treat.

Gupta says that it was already possible to obtain myeloma cells from patients and test whether they are sensitive to venetoclax directly in the laboratory. But this isn’t practical for most clinics in cancer centers elsewhere.

“In contrast, the B cell phenotype can easily be assessed by flow cytometry, a technique that is routinely performed in clinical labs,” Gupta says. “So we are attempting to refine and validate our panel of flow cytometry markers, so that it can be used to easily and accurately predict which patients are sensitive to venetoclax.”

Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Divide and conquer vs lung cancer

Doctors are using a “divide and conquer” strategy against lung cancer, and in some corners of the battlefield, it’s working. A few mutations – genetic alterations in the tumor that don’t come from the patient’s normal cells — have been found for which drugs are effective in pushing back against the cancer.

However, most lung tumors do not have one of these mutations, and response rates to conventional chemotherapy in patients with advanced lung cancer are poor. Generally, only around 20 percent of patients show a clinical response, in that the cancer retreats noticeably for some time.

Johann Brandes and colleagues at Winship Cancer Institute have been looking for biomarkers that can predict whether an advanced lung tumor is going to respond to one of the most common chemotherapy drug combinations, carboplatin and taxol.

“The availability of a predictive test is desirable since it would allow patients who are unlikely to benefit from this treatment combination to be spared from side effects and to be selected for other, possibly more effective treatments,” Brandes says.

Brandes’ team’s data comes from looking at patients with advanced lung cancer at the Atlanta VAMC from 1999 to 2010. In a 2013 paper in Clinical Cancer Research, the team looked at a protein called CHFR. It controls whether cells can reign in their cycles of cell division while being bombarded with chemotherapy.

In this group being treated with carboplatin and taxol, patients who had tumors that measured low in this protein lived almost four months longer, on average, than those who had tumors that were high (9.9 vs 6.2 months).

His team takes a similar approach in a new paper published in PLOS One. Postdoc Seth Brodie is the first author of the PLOS One paper; he is also co-first author of the CHFR paper along with Rathi Pillai. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Personalized molecular medicine part 2

This is a continuation of the post from last week on the early-onset epilepsy patient, whom doctors were able to devise an individualized treatment for. The treatment was based on Emory research on the molecular effects of a mutation in the patient’s GRIN2A gene, discovered through whole exome sequencing.*

For this patient, investigators were able to find the Ray Ban Baratas cause for a previously difficult to diagnose case, and then use a medication usually used for Alzheimer’s disease (memantine) to reduce his seizure frequency.

Last week, I posed the question: how often do we move from a disease-causing mutation to tailored treatment? Read more

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment