New research from Memorial Sloan Kettering Cancer Center (MSK) highlights advancements in cancer treatment, including strategies to overcome drug resistance in breast cancer, expand the use of radiotherapy in prostate cancer, refine radiation therapy techniques for spinal tumors, and utilize proton therapy for head and neck cancers.
Overcoming Breast Cancer Drug Resistance with CDK2 Inhibition
Estrogen receptor-positive breast cancer, the most common type, is often treated with hormone therapy combined with CDK4/6 inhibitors. However, the duration of response to this combination varies significantly, with some patients experiencing disease control for years while others progress within months. A research team led by Sarat Chandarlapaty, MD, PhD, analyzed samples from thousands of breast cancer patients to understand the mechanisms of resistance.
The study revealed that tumors with a short-lived response to treatment frequently harbored mutations in the p53 gene. Further investigation identified CDK2 as a key enzyme enabling p53-mutated tumors to resume growth. In laboratory models, blocking both CDK2 and CDK4/6 induced a deep, arrested state in these tumors. Clinical trials at MSK are now underway to test CDK2 inhibitors in combination with CDK4/6 inhibitors. According to Dr. Chandarlapaty, this approach could significantly benefit patients with p53 mutations or related genetic alterations.
The findings were published in Cancer Cell.
Expanding Prostate Cancer Radiotherapy with 177Lu-PSMA-617
A Phase 3 clinical trial led by Michael Morris, MD, demonstrated that 177Lu-PSMA-617 (Pluvicto®) improved disease control and quality of life in patients with metastatic castration-resistant prostate cancer compared to second-line hormonal approaches. The trial involved 468 patients and showed that 177Lu-PSMA-617 prolonged progression-free survival compared to second-generation androgen receptor pathway inhibitors (ARPIs).
177Lu-PSMA-617, approved by the FDA in 2022 for patients who have progressed despite ARPI and taxane-based chemotherapy, selectively targets the PSMA protein on cancer cells, delivering radiation directly to the tumor. The new trial results suggest expanding its use to patients who have not yet received taxane therapy. Dr. Morris noted that while the standard approach involves ARPI followed by taxane, some patients delay taxane due to side effects, switching to different hormonal therapies instead. The trial indicates that proceeding directly to 177Lu-PSMA-617 may offer improved outcomes and fewer side effects.
The results were published in The Lancet.
Optimizing SBRT Dosing for Spinal Metastasis
Researchers at MSK presented findings at the American Society for Radiation Oncology (ASTRO) Annual Meeting regarding radiation treatment advances. A study led by Christopher Jackson, MD, MS, and Daniel Higginson, MD, focused on stereotactic body radiation therapy (SBRT) for spinal metastasis. SBRT is a targeted radiation therapy that minimizes damage to healthy tissue but carries a risk of radiation myelitis, a rare complication causing spinal swelling and neurological symptoms.
The team reviewed medical records of over 1,400 patients who received SBRT for spinal metastasis to identify the optimal radiation dose that maximizes treatment response while minimizing the risk of radiation myelitis. The study established new radiation dose guidelines to inform SBRT delivery for patients with spinal metastasis globally.
The study was published in the International Journal of Radiation Oncology, Biology, Physics.
Proton Therapy for Recurrent Head and Neck Cancers
A Phase 2 clinical trial led by Nancy Lee, MD, demonstrated the effectiveness of proton therapy in treating recurrent head and neck cancers that have previously received radiation therapy. These cancers are challenging to treat with additional radiation due to resistance and the risk of toxicity to surrounding healthy tissue.
Proton therapy, an advanced form of radiation using charged particles, reduces the dose to normal tissues. The trial showed that proton therapy stopped the progression of recurrent cancers and extended survival. After five years, cancer was controlled in 38% of patients, and 32% had survived. Dr. Lee emphasized the remarkable results given the patients' prior treatments and disease severity, suggesting that proton therapy is an effective and less toxic alternative to standard radiation therapy.
The study was published in the International Journal of Radiation Oncology, Biology, Physics.
