Cancer News and Discussions

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Base editing: Revolutionary therapy clears girl's incurable cancer
Source: BBC.com
A teenage girl's incurable cancer has been cleared from her body in the first use of a revolutionary new type of medicine.

All other treatments for Alyssa's leukaemia had failed.

So doctors at Great Ormond Street Hospital used "base editing" to perform a feat of biological engineering to build her a new living drug.

Six months later the cancer is undetectable, but Alyssa is still being monitored in case it comes back.

Read more: https://www.bbc.com/news/health-63859184
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Experimental cancer therapy shows success in more than 70% of patients in global clinical trials
https://medicalxpress.com/news/2022-12- ... ients.html
by The Mount Sinai Hospital
A new therapy that makes the immune system kill bone marrow cancer cells was successful in as many as 73% of patients in two clinical trials, according to researchers from The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be enlisted to fight off diseases—to kill multiple myeloma cells. The researchers described this strategy as "bringing your army right to the enemy."

The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.

Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in the New England Journal of Medicine, established two recommended doses that were tested in the Phase 2 trial. The results of the Phase 2 trial were reported at the American Society of Hematology annual meeting on Saturday, December 10. The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.
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Researchers identify key metabolic regulators of drug resistance in the fight against pancreatic cancer
https://medicalxpress.com/news/2022-12- ... eatic.html
by Rebecca Brierley, University at Buffalo
Researchers from the University at Buffalo School of Pharmacy and Pharmaceutical Sciences recently published in Molecular & Cellular Proteomics, describing their work in identifying key metabolic regulators involved in cancer cell resistance to gemcitabine (Gem), a standard-of-care chemotherapy for pancreatic dual adenocarcinoma (PDAC), the most lethal type of pancreatic cancer.

Robert M. Straubinger, Ph.D., UB Distinguished Professor, and Jun Qu, Ph.D., Professor, both of the Department of Pharmaceutical Sciences, led the research, which included William J. Jusko, Ph.D., SUNY Distinguished Professor, and several of his lab members.

Gemcitabine resistance (GemR) can develop clinically during chemotherapy, resulting in poor patient prognosis. Understanding the molecular mechanisms of Gem resistance has been challenging.

Straubinger and Qu collaborated on the application of a cutting-edge comprehensive, quantitative proteomic analysis approach to identify key metabolic regulators of Gem resistance in PDAC. Their team systematically examined PDAC cancer cells and identified several therapeutic vulnerabilities of drug resistance that could be targeted to improve therapeutic outcomes for PDAC patients experiencing Gem resistance.

Pancreatic adenocarcinoma does not respond well to current treatments or to newer immunotherapies that have worked well in some cancers. Gem is the mainstay drug for PDAC patients but provides only modest survival benefits. Clinically, development of Gem resistance can be rapid and compromises its efficacy.
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Moderna's mRNA Skin Cancer Vaccine Shows Early Promise in a New Study
https://time.com/6240538/mrna-cancer-vaccine-moderna/
By Alice Park
December 13, 2022 9:46 AM EST
Coming off the success of its mRNA vaccine for COVID-19, Moderna announced on Dec. 13 that it achieved encouraging results when it turned its vaccine technology against cancer.

The company reported in a release that among 157 people with stage 3 or stage 4 melanoma, a personalized cancer vaccine that Moderna developed with Merck—created using mRNA genetic material from each patient’s respective tumors—reduced the risk of recurrence or death by 44% compared to standard care.

“For the first time ever, we have evidence that it’s possible to develop a functional immune response that can treat patients’ cancer from a randomized controlled trial,” says Dr. Stephen Hoge, president of Moderna.
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Cancer Treatments Boosted by Immune-cell Hacking
by Heidi Ledford
December 15, 2022

Introduction:
(Nature) Elaborately engineered immune cells can not only recognize cancer cells, but also evade defences that tumours use to fend off attacks, researchers have found.

Two studies published today in Science1,2 build on the success of chimeric antigen receptor (CAR)-T cancer therapies, which use genetically altered T cells to seek out tumours and mark them for destruction. These treatments have the potential to lead to long-lasting remission, but are not successful for everyone, and have so far been effective against only a small number of cancers.
Read more here: https://www.nature.com/articles/d41586-022-04465-y
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Rethinking how cancer cells evade targeted therapy
https://medicalxpress.com/news/2022-12- ... erapy.html
by University of California, San Francisco
Glioblastomas (GBMs) are incurable brain tumors with a prognosis of about one-and-a half years on average. They are highly resistant to treatment and have defied all attempts at precision therapy.

In their study publishing December 20 in Nature Cancer, first author Lin Wang, Ph.D. and senior author Aaron Diaz, Ph.D., found that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. They found that some cells shift to a mesenchymal, radiation-resistant phenotype (state) as a stress response following standard therapy. 

"We asked if there is another mechanism that explains therapeutic resistance," said Diaz, associate professor of neurological surgery at the UCSF Weill Institute for Neurosciences. "Our study concludes that, rather than a genetic evolution, there is a phenotypic plasticity or transition which allows these cells to evade therapy."

To identify what drives treatment resistance to standard therapy, as well as the cellular source of recurrent disease, UCSF researchers used single-nucleus RNA, open-chromatin, spatial profiling to analyze 86 primary-recurrent, patient-matched, paired GBM specimens. This unprecedented cohort represented decades of biobanking at UCSF.

With access to thirty years' worth of GBM's, the scientists were able to present novel cell-intrinsic and cell-extrinsic targets as well as a single-cell multi-omics atlas of GBM under therapy. This was the first time that researchers were able to comprehensively map intra-cellular signaling in the tumor-anatomical niches of recurrent GBM and identify novel cell-extrinsic therapeutic targets.  

The 86 specimens contained the cellular tumor and adjacent non-malignant tissue from the surgical margin. This unique cohort enabled Diaz and his team to analyze communications between malignant and non-malignant glia. They found that cells in this surgical margin acted as niches of recurrence where non-malignant glia were broadcasting pro-growth signals that influenced the tumor cells to regrow. These paracrine (cell extrinsic) signals stimulated the activator protein (AP1) pathway, leading to mesenchymal transition, therapy resistance and tumor recurrence.
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Researchers publish findings that could help prevent side effects for breast cancer patients
https://medicalxpress.com/news/2022-12- ... ancer.html
by Indiana University School of MedicineNational Institutes of Health
Researchers at Indiana University School of Medicine are learning more about ways to prevent serious side effects from chemotherapy used to treat breast cancer patients. The work done by the Schneider lab at the Vera Bradley Foundation Center for Breast Cancer Research at the IU Melvin and Bren Simon Comprehensive Cancer Center and led by Xi Wu, Ph.D. was recently published in Nature Communications.

Anthracyclines belong to a class of chemotherapy agents used to treat a variety of cancers and remain an important part of therapy for patients with high-risk breast cancer. While effective in improving cure rates, they can also cause serious heart damage, including heart failure, which is often irreversible.

"This is of crucial clinical importance for breast cancer patients as there are no proven strategies for prevention or interventions for cardiotoxicity," said Wu, a former Vera Bradley Foundation Scholar who is the first author of the publication.
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New bacterial therapy approach to treat lung cancer

by Holly Evarts, Columbia University School of Engineering and Applied Science
https://medicalxpress.com/news/2022-12- ... ancer.html
Lung cancer is the deadliest cancer in the United States and around the world. Many of the currently available therapies have been ineffective, leaving patients with very few options. A promising new strategy to treat cancer has been bacterial therapy, but while this treatment modality has quickly progressed from laboratory experiments to clinical trials in the last five years, the most effective treatment for certain types of cancers may be in combination with other drugs.

Columbia Engineering researchers report that they have developed a preclinical evaluation pipeline for characterization of bacterial therapies in lung cancer models. Their new study, published December 13, 2022, by Scientific Reports, combines bacterial therapies with other modalities of treatment to improve treatment efficacy without any additional toxicity. This new approach was able to rapidly characterize bacterial therapies and successfully integrate them with current targeted therapies for lung cancer.

"We envision a fast and selective expansion of our pipeline to improve treatment efficacy and safety for solid tumors," said first author Dhruba Deb, an associate research scientist who studies the effect of bacterial toxins on lung cancer in Professor Tal Danino's lab in Biomedical Engineering, "As someone who has lost loved ones to cancer, I would like to see this strategy move from the bench to bedside in the future."

The team used RNA sequencing to discover how cancer cells were responding to bacteria at the cellular and molecular levels. They built a hypothesis on which molecular pathways of cancer cells were helping the cells to be resistant to the bacteria therapy. To test their hypothesis, the researchers blocked these pathways with current cancer drugs and showed that combining the drugs with bacterial toxins is more effective in eliminating lung cancer cells. They validated the combination of bacteria therapy with an AKT-inhibitor as an example in mouse models of lung cancer.
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BioNTech says it will start cancer vaccine trials in the UK from September
Published Fri, Jan 6 20238:27 AM ESTUpdated Fri, Jan 6 20238:54 AM EST
https://www.cnbc.com/2023/01/06/biontec ... ember.html
LONDON — The U.K. government on Friday announced a partnership with German firm BioNTech

to test potential vaccines for cancer and other diseases, as campaigners warned any breakthrough must remain affordable and accessible.

Cancer patients in England will get early access to trials involving personalized mRNA therapies, including cancer vaccines, which aim to spur the immune system to attack harmful cells.

They will be administered to early and late-stage patients and target both active cancer cells and preventing their return.

BioNTech will set up new research and development centers in the U.K., with a lab in Cambridge and headquarters in London, and aim to deliver 10,000 therapies to patients from September 2023 until the end of the decade.

The company developed one of the most widely-distributed Covid-19 vaccines alongside U.S. pharma firm Pfizer
. Its CEO, Ugur Sahin, said it had learned lessons from the coronavirus pandemic about collaboration between the British National Health Service, academics, regulators and the private sector in the development of drugs that it was applying now.
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