Verzenio (Abemaciclib)-Higher for CDK4 over CDK6 & Continuous daily dosing
#Manufacturer: EliLilly
#Sales: Over $1 billion annually
#Indication: hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer
#Mechanism of Action: Verzenio inhibits CDK4 and CDK6, proteins that drive the cell cycle forward by phosphorylating the retinoblastoma protein (Rb). This inhibition prevents the progression from the G1 phase to the S phase in the cell cycle, leading to cell cycle arrest and potentially inducing apoptosis in cancer cells.
#CombinationTherapies:
Verzenio + Letrozole
Verzenio + Anastrozole
Verzenio + Fulvestrant
Verzenio + Exemestane
Verzenio + Tamoxifen
Verzenio + LHRH Agonists such as goserelin
Verzenio + Chemotherapy like doxorubicin or paclitaxel
Verzenio + PI3K Inhibitors such as alpelisib (Piqray) target the PI3K/AKT/mTOR pathway
Verzenio + mTOR Inhibitors such as everolimus inhibit the mTOR pathway
Verzenio + HER2-Targeted Therapy such as trastuzumab (Herceptin) or Pertuzumab (Perjeta)
Verzenio + PARP Inhibitors such as Olaparib (Lynparza)
Verzenio + Immune Checkpoint Inhibitors such as Pembrolizumab (Keytruda)
Verzenio + Epigenetic Modulators such as HDAC inhibitors (e.g., Vorinostat) or DNMT inhibitors
Verzenio + Anti-Angiogenic Agents such as Bevacizumab (Avastin)
Verzenio + Metformin possibly through AMPK activation and mTOR inhibition
#SideEffects: Diarrhea, Neutropenia, Fatigue, Nausea and Vomiting, Abdominal Pain, Infections, Decreased Appetite, Anemia, Thrombocytopenia, Increased Liver Enzymes, etc.
Severe Side Effects: Severe Diarrhea, Severe Neutropenia (low white blood cell count), Hepatotoxicity, Pulmonary Embolism, Interstitial Lung Disease.
#Goals of a multi-approach:
to inhibit cell cycle progression
to enhance DNA damage in cancer cells
to boost the immune response against cancer
to prevent cancer cells from finding alternative pathways for growth
to inhibit parallel pathways, providing a more comprehensive blockade of cancer cell proliferation
to reprogram cancer cells to a less aggressive state, potentially enhancing the effects of CDK4/6 inhibitors
to complement the action of Verzenio by cutting off the tumor’s blood supply while inhibiting cell cycle progression
to provide metabolic stress to cancer cells, enhancing the effects of Verzenio
a sufficient amount of the drug reaches the tumor site intact, improving its therapeutic efficacy
etc.
