April 13, 2024

Ovarian Cancer Drugs: Progress and Challenges

Ovarian cancer affects thousands of women each year. Researchers and medical professionals have made progress in developing ovarian cancer drugs but there are still challenges that need to be addressed. This article explores some of the key ovarian cancer drugs currently available as well as ongoing research efforts.

Platinum-Based Chemotherapy

Platinum-based chemotherapy has been a mainstay of ovarian cancer treatment for decades. Drugs like carboplatin and cisplatin work by damaging the DNA of cancer cells, which promotes cell death. Unfortunately, many tumors develop resistance to these drugs over time. However, when given in combination with other chemotherapy drugs at the outset, platinum drugs can significantly improve survival rates. For example, the combination of carboplatin and paclitaxel is a standard first-line treatment for ovarian cancer. On average, this regimen provides 16-24 months of progression-free survival.

Advances in Targeted Therapy

While chemotherapy remains important, researchers have made strides in developing newer targeted therapies. Bevacizumab is an anti-angiogenic drug that works by inhibiting the growth of new blood vessels that feed tumors. Adding bevacizumab to standard chemotherapy was shown to extend progression-free survival by 4 months on average in front-line ovarian cancer. However, the true benefit of bevacizumab may be most apparent in certain tumor subtypes expressing high levels of vascular endothelial growth factor (VEGF).

Another targeted approach involves using PARP inhibitors. These drugs take advantage of defective DNA repair pathways in tumors with BRCA gene mutations and other homologous recombination deficiencies. Three PARP inhibitors – olaparib, niraparib, and rucaparib – have been approved to maintain response for ovarian cancer in remission or for recurrent disease. Olaparib, the first PARP inhibitor approved, demonstrated a near tripling in progression-free survival compared to placebo maintenance therapy. PARP inhibitors are also being explored in earlier-line settings, both as maintenance therapy and in combination with other agents.

Immunotherapy Holds Promise

While chemotherapy and targeted agents have advanced treatment, ovarian cancer often evades and suppresses the immune system to promote growth and spread. Immunotherapy seeks to counteract these effects to stimulate anti-tumor immunity. Drugs called PD-1/PD-L1 inhibitors work by blocking interaction between these immune checkpoint proteins to unleash T cells against cancer cells.

In recurrent platinum-resistant disease, the PD-L1 inhibitor avelumab showed promising responses alone or combined with chemotherapy in early trials. Larger phase 3 studies are currently underway combining avelumab with chemotherapy versus chemotherapy alone. Other immunotherapies under investigation include vaccines targeting tumor-associated antigens like NY-ESO-1. Adoptive cell transfer using genetically engineered T cells is also an area of active research.

Although more data is needed, initial results suggest immunotherapy could widen treatment options – especially when combined judiciously with other modalities before resistance develops. Ongoing combination trials will help define optimal integration of immunotherapy into the ovarian cancer treatment algorithm moving forward.

Challenges of Drug Resistance and Recurrence

While newer drugs are improving outcomes, resistance and recurrence still pose formidable challenges. Even initially responsive tumors often relapse with mutations allowing survival and growth mechanisms to reactivate. Platinum drugs can lose effectiveness as residual tumor cells evolve workarounds. Targeted therapies like PARP inhibitors may maintain benefit for 18-24 months on average before resistance emerges.

One strategy aims to delay or prevent resistance by combining drugs that work through distinct mechanisms. For example, researchers are studying sequential or concurrent use of platinum chemotherapy, anti-angiogenesis drugs, immunotherapy, and PARP inhibitors to continually pressure tumors in complementary ways. Biomarker-driven methods could also help match tumors to the specific agents they are most sensitive to at different stages. Continued probing of resistance mechanisms remains critical to guide these combination approaches.

Continued Innovation on the Horizon

With major gains made but important unfinished business, ovarian cancer research marches forward. Efforts are ongoing to define molecular subtype signatures linked to behavior and drug sensitivity. Companies are developing new classes of targeted agents against tumor dependencies like folate receptors and LSD1 enzymes. Additionally, cell and gene therapy holds long-term promise. For example, chimeric antigen receptor (CAR) T cells are under investigation for fighting ovarian cancer in preclinical models.

Looking ahead, advances in ovarian cancer treatment will require continued innovation across multiple fronts. Greater focus on early detection by objective symptom tracking and novel biomarkers could shift more cases to curative settings. Enhanced team science collaborations will be instrumental to efficiently translate new knowledge into improved patient outcomes, management of resistant disease, and ultimately more survivors. With committed effort and resources, overcoming ovarian cancer remains an achievable goal.

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  1. Source: Coherent Market Insights, Public sources, Desk research

2. We have leveraged AI tools to mine information and compile it