As the world began to emerge from the grip of COVID-19, discoveries in cancer treatment research yielded potential therapies for a variety of cancer types.

Here are some of these potential breakthroughs that show promise for the future of oncological care.

 

SHP656 for patients with glioblastoma

Glioblastomas are among the most common—and potentially deadly—brain cancers affecting adults.

Circadian rhythm is influenced by several transcription factors, such as CLOCK and BMAL1, and genes, including CRY1 and CRY2, according to research published in Proceedings of the National Academy of Sciences (PNAS).

Miller S, Kesherwani M, Chan P, et al. CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy. Proc Natl Acad Sci USA. 2022;119(40):e2203936119.

 

Self-renewing glioblastoma stem cells (GSCs) are highly dependent on CLOCK and BMAL1 for their malignant properties, according to PNAS. A compound, SHP656, was shown to suppress GSC growth and survival in cell culture; researchers believe it acts to stabilize CRY genes, inhibiting the actions of CLOCK-BMAL1 transcription factors.

Oral administration of SHP656 extended the survival period of mice with GSC intracranial implants. Given that GSCs are resistant to standard therapies like chemotherapy and radiation, the introduction of SHP656 may help usher in a new treatment era for patients with glioblastomas.

 

Dostarlimab eliminates rectal cancer

It’s a treatment result that sparked interest and hope around the world: In a very small trial, the drug dostarlimab (Jemperli) was found to completely eliminate rectal cancer in all study participants, as reported by CBS News.

Yates B. Cancer trial shows ‘unprecedented’ results as 100% of participants see cancer disappear. CBS News. June 11, 2022.

Each of the participants previously tried other therapies, such as chemotherapy, with no success.

 

During the trial, each of the 18 patients took dostarlimab once every 3 weeks over 6 months. They were all in similar stages of cancer, which was locally advanced but not spread beyond the rectum. By the trial’s end, cancer was undetectable by physical examination, endoscopy, and imaging studies, such as PET scans, in all patients.

 

Two-pronged treatment helps immunotherapy-resistant patients

A study from the UK found a new possible treatment combination for patients demonstrating resistance to immunotherapy, according to an article published by The Guardian.

Gregory A. New cancer treatment offers hope to patients out of options. The Guardian. August 22, 2022.

In the study, the drug guadecitabine was combined with the immunotherapy drug pembrolizumab to help reverse cancer’s immunotherapy resistance.

 

Guadecitabine is a next-generation DNA hypomethylating agent. When it was combined with pembrolizumab, patients who were previously thought to have exhausted all treatment options survived much longer than anticipated. Included in the research were patients with various forms of cancer, including bowel, breast, lung, and prostate cancer.

Patients received guadecitabine injections every 3 weeks for 4 days in a row. The trial itself lasted for 3 years; the results indicated that 37% of trial participants had complete disease remission after taking the drug combination.

This study was a phase 1 trial. Further research on this treatment combination is underway, according to The Guardian.

 

 

ERX-41 kills several hard-to-treat cancers, including triple-negative breast cancer

Many cancer treatments rely on actional therapeutic targets to alter cancer cells and ultimately cause remission. A small molecule, ERX-41, was discovered as researchers searched for such targets in triple-negative breast cancer cases, as reported in a Nature Cancer article.

Liu X, Viswanadhapalli S, Kumar S, et al. Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress. Nat Cancer. 2022;3(7):866-884.

 

Unlike other treatments, ERX-41 binds to lysosomal acid lipase A (LIPA) resulting in endoplasmic reticulum (ER) stress. This eventually resulted in cancer cell death via autophagy, apoptosis, necroptosis, or immunogenic cell death.

This drug has not been evaluated in human studies. It kills TNBC cells in vitro, but it is not yet known if it is safe or effective in human beings. Researchers hope that further study will yield treatment options featuring ERX-41 and its ability to include cellular death.

 

Second CTLA-4 immune checkpoint inhibitor approved for unresectable liver cancer

Patients living with unresectable hepatocellular carcinoma, the most common form of liver cancer, have an additional treatment option. In late 2022, the FDA approved the drug tremelimumab (Imjudo) for use in combination with durvalumab (Imfinzi) to create the single tremelimumab regular interval durvalumab (STRIDE) regimen, as reported by AstraZeneca.

Imjudo (Tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. AstraZeneca. October 24, 2022.

 

Under the regimen, patients take a single 300mg dose of CTLA-4 immune checkpoint inhibitor tremelimumab along with 1500mg of anti-PD-L1 antibody durvalumab, followed by subsequent doses of durvalumab every 4 weeks. In clinical trials, this regimen reduced patients’ risk of death by 22% compared to standard treatment with sorafenib.