Precision targeting provides new insights into therapy-resistant cancers

March 6, 2017 by Lorena Anderson, University of California - Merced
Precision targeting provides new insights into therapy-resistant cancers
UC Merced researcher Fabian V. Filipp in the lab. Credit: UC Merced Systems Biology and Cancer Metabolism Laboratory

The National Cancer Institute's "cancer moonshot" tasks researchers with, among advancing other new biotechnologies, delving into immunotherapy and epigenomic analysis.

UC Merced professor Fabian V. Filipp is doing his part, further developing his work on precision targeting of cancers and personalized medicine.

Filipp has already mapped the genetic landscape of melanoma and found a drug that could be effective in battling the deadly skin , and has now identified epigenetic master regulators that control cancer published today in Oncotarget, Cancer Metastasis Review, and Oxford Academic Press.

"The essence of precision medicine is to understand, which drug targets are effective given each person's unique genetic and epigenetic makeup," Filipp said.

What many people don't know is that there is more to the genes than what we might see molecularly.

"There is a hidden layer of regulation controlling the activity of genes without changing the core code of our DNA. This field of study is called epigenetics," he said.

Filipp's approach to precision targeting shows that if researchers can regulate hormone receptors and epigenetic factors at the same time, they can control cancer.

"That's why molecular understanding of epigenetic mechanisms underlying the development of cancer is of critical importance," he said.

Professor Fabian V. Filipp working on cancer epigenomics and precision targeting of malignant melanoma at UC Merced Systems Biology and Cancer Metabolism Laboratory. Credit: UC Merced Systems Biology and Cancer Metabolism Laboratory

The 'yin and yang' of cancer

According to latest genomic insights, researchers compare the delicate epigenomic homeostasis to yin and yang: Complementary forces keep each other in check. If one force overtakes the systems is out of equilibrium. For the cells this means either unlimited growth, cancer, or death. Without doubt, once we have a better understanding of epigenomic regulation, we can design drugs that counterregulate these factors.

Today, his research group published several research articles on precision targeting of therapy-resistant cancer, including cover studies in Oncotarget, Springer's Cancer Metastasis Reviews, and Oxford's Briefings in Functional Genomics, as well as recent work in Nature Publishing's Scientific Reports, and Wiley's Pigment Cell Melanoma Research.

Filipp's Systems Biology and Cancer Metabolism Lab in the School of Natural Sciences at UC Merced identified such an epigenetic factor, which the researchers named Jumonji because of its "magic and mysterious roles in cancer and cellular development."

"Epigenomic modifiers have the ability to modulate our genetic readouts—they can emphasize or silence genes," Filipp said. "If an epigenomic modifier is dysregulated in cancer, it might switch on oncogenes (genes that in certain circumstances transform cells into tumor cells) or shut down tumor suppressors. Both events will transform cells into tumor cells. In addition to genomic changes, epigenomic changes also contribute to the ability of cancer cells to evade therapy."

"We are all proud of professor Filipp's accomplishments," Vice Chancellor for Research Samuel Traina said. "He exemplifies the attributes of a great UC professor."

In addition to prolific publishing, Filipp recently delivered guest lectures at the University of Maryland School of Medicine's Greenbaume Cancer Center and the Pan-American Society for Pigment Cell Research's conference entitled "Pigment Cells, Their Responses, and the Generation of Diversity" conference, both in Baltimore, where he chaired a session on melanoma metabolism. He also received several awards recently, including Pan-American Society for Pigment Cell Research's Estela Medrano Young Investigator Award; the University of California Office of the President Cancer Research Coordinating Committee Award and the Margo F. Souza San Joaquin Valley Mentor Leadership Award.

In research science, Filipp is especially concerned with promoting advanced graduate training and student mentoring. Filipp has developed the first advanced training course on , cancer metabolism and metabolic flux analysis for graduate students in the Quantitative Systems Biology group at UC Merced, where he brought guest speakers from Europe. Last year, he promoted hands-on training in cancer systems biology for UC Merced undergraduates and Merced high school students, and plans to do the same this year.

"It is a special fulfilment to foster young careers and see our research talent grow in the Central Valley of California," Filipp said.

Explore further: Epigenetic changes promoting cancer metastasis identified

More information: Stephen Wilson et al. The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells, Oncotarget (2017). DOI: 10.18632/oncotarget.15681

OUP accepted manuscript, Briefings in Functional Genomics (2017).
DOI: 10.1093/bfgp/elx001

Jessamy C. Tiffen et al. EZH2 as a mediator of treatment resistance in melanoma, Pigment Cell & Melanoma Research (2016). DOI: 10.1111/pcmr.12481

Related Stories

Epigenetic changes promoting cancer metastasis identified

December 21, 2016
Latest University of Otago research is shedding new light on why and how cancer cells spread from primary tumours to other parts of the body. This phenomenon – known as metastasis – causes about 90 per cent of all cancer ...

Study reveals how melanoma spreads

February 8, 2017
Cancerous tumors are voracious. Once they have consumed all the oxygen and nutrients in the original tumor site, the cancer cells travel to other parts of the body (metastasize) to find more nourishment.

Study identifies potential combination therapy for ovarian cancer

October 28, 2016
A new study has identified an effective combination therapy for treating ovarian cancer cells.

Scientists find three subgroups in a children's brain cancer, identify druggable targets

December 12, 2016
Multi-institutional researchers investigating an incurable brain cancer in children have discovered three distinct subgroups of disease and identified promising drugs to target each type.

Researchers define how cancer cell of origin controls invasive and metastatic properties of tumor cells

November 24, 2016
Researchers at the Université libre de Bruxelles, ULB define for the first time how the cancer cell of origin controls invasive and metastatic properties of tumor cells.

Study finds breast and ovarian cancer may have similar origins

May 23, 2016
While breast cancer is the most common cause of cancer death in women worldwide, ovarian cancer also is a significant source of mortality as the fifth leading cause of cancer death among women. These facts reflect the continued ...

Recommended for you

Scientists block the siren call of two aggressive cancers

January 23, 2018
Aggressive cancers like glioblastoma and metastatic breast cancer have in common a siren call that beckons the bone marrow to send along whatever the tumors need to survive and thrive.

'Hijacker' drives cancer in some patients with high-risk neuroblastoma

January 23, 2018
Researchers have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases and have used a new approach to show how the cancer genome "hijacks" DNA that regulates other genes. The resulting insights ...

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Study: Cells of three advanced cancers die with drug-like compounds that reverse chemo failure

January 23, 2018
Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggressive cancers—ovarian, prostate and breast.

Researchers identify a protein that keeps metastatic breast cancer cells dormant

January 23, 2018
A study headed by ICREA researcher Roger Gomis at the Institute for Research in Biomedicine (IRB Barcelona) has identified the genes involved in the latent asymptomatic state of breast cancer metastases. The work sheds light ...

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.