Overview

Introduction and Overview

Hereditary cancers are those driven by genetic mutations passed down through families. These mutations increase the risk of certain cancer types and are often linked to well-known genes such as **BRCA1**, **BRCA2**, **APC**, **CDKN2A**, and **Lynch Syndrome (MLH1, MSH2, MSH6, PMS2)**. Understanding these genetic risks allows for early detection, preventive measures, and targeted therapies that improve survival rates and reduce cancer recurrence.

Common Hereditary Cancers

1. Breast and Ovarian Cancer (BRCA1, BRCA2)

Mutations in **BRCA1** and **BRCA2** are linked to significantly higher risks of breast and ovarian cancer. Women with BRCA mutations have up to an 87% risk of breast cancer and a 44% risk of ovarian cancer by age 70.

• **Preventive Strategies:** Prophylactic mastectomy, oophorectomy, enhanced MRI screening.
• **Targeted Therapies:** PARP inhibitors (Olaparib, Rucaparib) for targeted DNA repair inhibition.

2. Colorectal Cancer (Lynch Syndrome, APC gene mutations)

Lynch Syndrome is an inherited condition that increases the risk of colorectal cancer. APC gene mutations are associated with Familial Adenomatous Polyposis (FAP), which leads to numerous polyps in the colon and rectum.

• **Preventive Strategies:** Regular colonoscopy, polyp removal, aspirin therapy.
• **Targeted Therapies:** Immunotherapy with PD-1 inhibitors (Pembrolizumab) for MSI-high tumors.

3. Prostate Cancer (BRCA2, HOXB13)

Mutations in **BRCA2** and **HOXB13** are associated with aggressive forms of prostate cancer. Genetic testing can guide early detection and targeted treatment.

• **Preventive Strategies:** PSA testing, MRI screenings for high-risk individuals.
• **Targeted Therapies:** PARP inhibitors for BRCA2 mutations, hormone therapy for aggressive forms.

4. Pancreatic Cancer (BRCA2, PALB2, CDKN2A)

Pancreatic cancer is associated with mutations in **BRCA2**, **PALB2**, and **CDKN2A**. Genetic testing helps identify at-risk individuals for early intervention.

• **Preventive Strategies:** Regular MRI or endoscopic ultrasound for high-risk patients.
• **Targeted Therapies:** PARP inhibitors, targeted chemotherapy.

5. Gastric Cancer (CDH1 mutation)

Mutations in **CDH1** are linked to hereditary diffuse gastric cancer (HDGC), significantly increasing the risk of stomach cancer at a young age.

• **Preventive Strategies:** Prophylactic gastrectomy and regular endoscopic monitoring.
• **Targeted Therapies:** HER2-targeted therapy for HER2-positive gastric cancers.

6. Melanoma (CDKN2A, BAP1)

Inherited mutations in **CDKN2A** and **BAP1** increase the risk of melanoma and related skin cancers. Genetic screening can guide preventive measures.

• **Preventive Strategies:** Regular dermatological screenings and UV protection.
• **Targeted Therapies:** Immunotherapy (Pembrolizumab, Nivolumab) for metastatic melanoma.

Genetic Testing and Risk Assessment

Genetic testing identifies hereditary mutations, enabling early intervention and personalized treatment plans. Key tests include **Myriad MyRisk®, BRCA Analysis, Lynch Syndrome Panels**, and **Multi-Gene Panels** for comprehensive cancer risk assessment.

Preventive Strategies and Early Detection

Preventive strategies include enhanced surveillance, lifestyle modifications, and prophylactic surgeries for high-risk individuals. Early detection through regular screenings significantly improves survival rates in hereditary cancer patients.

Targeted Therapies for Hereditary Cancers

Targeted therapies focus on specific genetic mutations, offering personalized treatment options. These include:

• **PARP Inhibitors:** Effective for BRCA-mutated breast and ovarian cancers.
• **Immunotherapy:** Pembrolizumab for MSI-high colorectal cancers.
• **Tyrosine Kinase Inhibitors:** For EGFR and HER2 mutations in gastric and lung cancers.

Repurposed Cancer Drugs

Repurposed drugs that show efficacy in hereditary cancers include:

• **Metformin:** Shown to inhibit tumor growth in BRCA-mutated cancers.
• **Doxycycline:** Targets cancer stem cells and reduces metastasis.
• **Ivermectin:** Demonstrates anti-cancer properties through mitochondrial disruption.

Conclusion and Call to Action for Integrative Hereditary Cancer Care

Hereditary cancers present unique challenges but also opportunities for early detection and targeted therapies. Integrative oncology approaches, including natural substances, lifestyle modifications, and repurposed drugs, can enhance treatment outcomes. Genetic testing, preventive measures, and comprehensive care strategies are essential for managing hereditary cancer risk and improving patient survival.