The research, led by Dr. Li Ma, an oncologist at the University of Texas MD Anderson Cancer Center, was published in Science Translational Medicine.

How the Discovery Works

The team used a CRISPR-based screening method to explore which genes might drive cancer to spread to bones. They introduced 2,302 guide RNAs into cancer cells, each designed to increase the expression of a different gene. This process revealed that cancer cells with higher levels of the ACBP protein were significantly more likely to metastasize to the bones.

Further analysis of human cancer genomes confirmed this finding: patients with elevated ACBP levels were also more prone to bone metastases. In lab experiments, mice with higher levels of ACBP in their bloodstream saw cancer spread to their bones more often. However, when researchers treated these mice with two compounds—etomoxir and IKE—the cancer did not reach the bones.

Why This Matters

Bone metastasis is a major concern for cancer patients. It often causes chronic pain and increases the risk of fractures, making life significantly harder for those affected. While current treatments like bisphosphonates help manage symptoms, they don’t stop the spread of cancer to the bones.

This new research marks a step forward. The compounds tested—etomoxir, which disrupts fatty acid metabolism, and IKE, which triggers a type of cell death known as ferroptosis—were effective at reducing bone metastases in mice. By blocking the metabolic pathways cancer cells use to survive and spread, these compounds show promise for future therapies.

A Growing Focus on Bone Metastasis

The importance of this discovery is highlighted by recent news that Former President Joe Biden has aggressive prostate cancer that has metastasized to his bones. Although his medical team reports that the condition is under control, the case has brought renewed attention to the urgent need for better treatments targeting bone metastasis.

This research not only sheds light on the molecular mechanisms behind bone metastasis but also provides a strong foundation for developing targeted therapies that could dramatically improve outcomes for cancer patients in the future.

In a Phase 2b trial (Keynote-C34, also known as TACTI-003), Immutep demonstrated that combining eftilagimod with Merck & Co.’s checkpoint inhibitor Keytruda helped patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) — specifically those with low PD-L1 expression (combined positive score [CPS] <1) — achieve a median overall survival of 17.6 months when used as first-line therapy. These results come from Cohort B of the study, which included 31 patients. Notably, the trial did not include a direct active control group. According to Immutep, the 17.6-month median survival exceeds historical benchmarks from standard-of-care treatments. Jefferies analyst David Stanton described the annual survival results as “impressive” in a statement.
Immutep plans to engage with the FDA to discuss potential approval of eftilagimod for first-line treatment of PD-L1-negative HNSCC, supported by its existing fast-track designation. CEO Marc Voigt confirmed that the company will meet with regulatory authorities to evaluate next steps toward potential approval of eftilagimod in combination with Keytruda.

This combination therapy presents a unique value proposition: it offers a chemotherapy-free immunotherapy alternative for PD-L1-negative patients, a group currently limited to chemo-based options. Eftilagimod, a LAG-3 fusion protein, activates antigen-presenting cells to boost immune response, according to Immutep.

The FDA first approved Keytruda with chemotherapy for initial HNSCC treatment in 2019, including patients with PD-L1-negative tumors. That approval was based on data showing a 23% reduction in mortality risk compared to Eli Lilly’s EGFR inhibitor Erbitux combined with chemotherapy, across all PD-L1 expression levels. Keytruda was also approved as a standalone treatment, but only for patients with CPS ≥1.

Post hoc analysis from the Keynote-048 trial revealed worse outcomes for PD-L1-negative patients treated with Keytruda and chemotherapy compared to Erbitux and chemotherapy. Median OS was 11.3 months for the Keytruda-chemo group vs. 10.7 months for Erbitux-chemo. Moreover, the risk of death was 21% higher in the Keytruda-chemo group for PD-L1-negative patients. However, researchers cautioned that the sample size for this subgroup was too small to draw definitive conclusions.

Against this backdrop, the 17.6-month median OS seen with the eftilagimod-Keytruda combination stands out, even though cross-trial comparisons should be interpreted cautiously.

These new survival data build on previous tumor response findings. Immutep earlier reported an objective response rate (ORR) of 35.5% in Cohort B of TACTI-003, including a 12.9% complete response rate. For comparison, Keynote-048 reported a 30.8% ORR and 2.6% complete response rate in the PD-L1-negative subgroup treated with Keytruda plus chemotherapy.

Voigt emphasized that the potential of this combination lies in delivering durable responses and significant survival benefits for a patient population in urgent need of more effective and tolerable options.

Immutep is aiming to serve the PD-L1-negative HNSCC segment, which it estimates comprises about 20% of all first-line HNSCC cases. Voigt noted that no current trials are investigating chemotherapy-free treatment approaches for this specific group.

Meanwhile, Keytruda continues to be evaluated in combination with other therapies. It is being paired with Exelixis’ investigational tyrosine kinase inhibitor, zanzalintinib, in the Phase 3 STELLAR-305 trial, which targets only PD-L1-positive HNSCC patients. Separately, Merus is conducting the Phase 3 LiGeR-HN1 trial, assessing its EGFR×LGR5 bispecific antibody petosemtamab with Keytruda in PD-L1-positive first-line HNSCC patients. Petosemtamab holds FDA Breakthrough Therapy designation.

According to the company, its procedure, which incorporates elements of DNA synthesis and nanopore-based molecular reading, has the potential to circumvent the time constraints of cycle-based sequencing as well as the similar challenges of discriminating actual signals from noise.

SBX, the innovative sequencing technology, represents the culmination of Roche’s strategic acquisitions. By acquiring Stratos Genomics in 2020, Roche gained access to the groundbreaking sequencing-by-expansion technology. This acquisition was complemented by the purchase of Genia Technologies in 2014, which brought with it an enormouslyl, single-molecule nanopore platform.

The integration of these two technologies has resulted in the development of SBX, a powerful tool that is poised to revolutionize the field of DNA sequencing.

At the beginning of the process, one individual strand of DNA is copied over into its counterpart, which is composed of As, Gs, Cs, and Ts, but these are the ones that are joined to a much bigger loop-shaped molecule that is programmed to correspond to its base.

As soon as the new molecule is finished being constructed, the DNA’s inner backbone is severed. In the process of the helix unwinding to a length up to fifty times greater than it was before, the loops eventually reach their full length. Because base pairs had previously been separated by a span of just a few atoms, this makes it possible to read each gene with a better degree of clarity.

The unfolded and amplified strand of DNA code, which is referred to as an Xpandomer, is then sent through the nanopores, where variations in electrical voltage correlate with every letter of the sequence of genes.

Roche Diagnostics CEO Matt Sause stated that the scientific foundation of SBX technology marks a major advancement, overcoming the constraints of current sequencing methods. His remarks were made in anticipation of the annual Advances in Genome Biology and Technology conference in Florida.

“By integrating and enhancing the two technologies, Roche’s SBX has created a differentiated approach, offering unparalleled speed, efficiency and flexibility,” he added. “The speed and accuracy of SBX has the potential to revolutionize the use of sequencing in research and healthcare.”

Despite the fact that the technology is still in the process of being developed and is not yet accessible for commercial use, Roche has said that the technique may one day be appropriate for sequencing the full genome and the exome, as well as parsing RNA. This would have uses in research laboratories and maybe even in clinical testing.

Additionally, the company said that it was scalable and capable of handling both big and small tasks, and announced its plan to get it off the ground next year.

Merck & Co., Inc. is a global pharmaceutical company based in New Jersey, USA. It was once part of the German Merck Group, founded in 1668. Known as Merck Sharp and Dohme or MSD in other parts of the world, the company is one of the world’s biggest manufacturers. It is among the world’s leading pharmaceutical companies, ranking usually in the first five drug makers globally in terms of sales.

Merck was established in 1891 as the American subsidiary company of the Merck Group. Merck grows and synthesizes drugs, vaccines, and biological and molecular treatments, also over animal healthcare. It has several best-selling drugs, such as cancer immunotherapy, anti-diabetic drugs, and vaccines for HPV and chickenpox, which collectively hold a high market value as of the period ending 2020.

The company said the drug achieved the primary endpoint of cutting the time to disease progression, lung transplantation, or death by half in a phase III trial involving 172 patients with the advanced stages of the illness on standard background therapy.
The disorder is present in approximately 40,000 patient populations across the country. An independent data monitoring committee has advised early termination of the study but would allow participants to continue to receive the treatment, Merck said.

Winrevair presently costs about $238,000 per year and was the first treatment from the class of drugs that targets a type of protein called activin. The drug accounts for $149 million in sales in the third quarter in Merck despite controversy over potential bleeding risk. “That’s why Winrevair seems safe to us despite potential side effects in severe patients — to which, most likely, it will restrict itself,” the Oppenheimer analysts said in a note earlier this month.