Utilizing AOH1996 with chemotherapy delivered via drug nanocarriers; an advanced novel approach for cancer treatment especially Inflammatory Breast Cancer

Abstract

Inflammatory Breast Cancer (IBC) is a rare disease but tends to be more aggressive than more common types of breast cancer. It accounts for 1–5% of new breast cancer cases. The treatment of IBC is comprised of chemotherapy in addition to targeted therapy as a neoadjuvant treatment, but it can be challenging to cure since IBC is a late-stage cancer. AOH1996 is a novel small molecule that has shown staggering results in inhibiting tumor growth in Phase Ⅰ clinical trials in multiple cancer types, including IBC. This compound is an orally active drug that was tested in vivo, inducing apoptosis in cancer cells without causing any discernable toxicity even at 6 times its effective dosage. Mechanistically, it enhances the PCNA-RPB1 interaction while interfering with TRC resolution, which results in DNA double-stranded breaks in a transcription-dependent manner. Besides apoptosis induction, AOH 1996 sensitizes tumor cells to cisplatin and topotecan treatments. Nonetheless, a promising approach to augmenting the efficacy of chemotherapeutic agents and decreasing their peripheral toxicity is delivering them via nanocarriers. Polymeric nanoparticles showed remarkable properties in delivering paclitaxel in the case of Abraxane (ABI-007). This paper investigates exploiting the AOH1996 drug with different chemotherapeutics delivered via nanocarriers to be used for most cancer types, especially IBC.